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

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

Dataset: Num of genes in input gene set: 15 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. Cacna1s Ankrd23 Ankrd1 Ankrd2 Smtnl1 Atp2a1 Casq1 Kat2b Aldoa Actc1 Mypn Num ofGenesinQueryGeneset:15.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Tcap Myl3 Ryr1 Ttn

Atp2a1 Ryr1 Casq1 Tcap Mypn Cacna1s Ttn Ankrd23 Smtnl1 Aldoa Actc1 Myl3 Ankrd2 Ankrd1 Kat2b Singletons CEM 1(158datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page1 Apobec2 Itgb1bp2 Cacna1s Ankrd23 Pde4dip Mybpc2 Cox6a2 Myom1 Ankrd2 Dhrs7c Ampd1 Smtnl1 Atp2a1 Trim54 Cmya5 Pgam2 Tmod4 Ckmt2 Klhl41 Casq1 Tnnc2 Actn2 Actn3 Aldoa Smpx Pygm Acta1 Actc1 Tnnt3 Pvalb Tpm2 Tnni2 Mylpf Mypn Myh2 Myh4 Rpl3l Eno3 Ldb3 Tcap Myot Nrap Myl1 Myl3 Ryr1 Hfe2 Ckm Neb Ttn Srl 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE6210 [12] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE31431 [34] GSE41759 [14] GSE12730 [24] GSE20577 [12] GSE41997 [6] GSE50813 [24] GSE24243 [6] GSE49122 [14] GSE11990 [20] GSE32316 [12] GSE24207 [73] GSE38257 [14] GSE51628 [15] GSE4786 [9] GSE13563 [6] GSE25295 [25] GSE32422 [6] GSE19616 [16] GSE4866 [10] GSE27309 [10] GSE9954 [70] GSE52358 [8] GSE12248 [83] GSE22307 [23] GSE28389 [20] GSE19079 [6] GSE16992 [48] GSE6055 [8] GSE41342 [26] GSE5800 [6] GSE36826 [12] GSE19517 [6] GSE10246 [182] GSE3501 [6] GSE31004 [8] GSE43242 [10] GSE11186 [33] GSE12993 [6] GSE15772 [8] GSE51883 [30] GSE7863 [16] GSE16377 [6] GSE30688 [9] GSE17739 [24] GSE5657 [20] GSE17825 [18] GSE9330 [8] GSE8498 [6] GSE41907 [7] GSE13224 [6] GSE46209 [21] GSE31561 [36] GSE21716 [28] GSE39897 [36] GSE28457 [24] GSE43373 [130] GSE33308 [10] GSE16110 [16] GSE5861 [6] GSE38822 [22] GSE8733 [24] GSE18567 [24] GSE51686 [9] GSE37191 [12] GSE38048 [20] GSE30865 [68] GSE43779 [6] GSE16777 [38] GSE16496 [102] GSE13071 [15] GSE56236 [12] GSE28417 [12] GSE11343 [19] GSE13032 [18] GSE35357 [12] GSE20726 [9] GSE4694 [6] GSE9368 [12] GSE11291 [60] GSE23006 [48] GSE15155 [12] GSE6591 [15] GSE23724 [8] GSE27628 [34] GSE59437 [30] GSE23782 [18] GSE7694 [12] GSE7475 [16] GSE9725 [16] GSE32020 [26] GSE21247 [60] GSE6686 [13] GSE38693 [8] GSE8513 [10] GSE3313 [24] GSE43381 [26] GSE19204 [6] GSE9460 [26] GSE19793 [32] GSE6837 [8] GSE35206 [14] GSE5313 [6] GSE18341 [30] GSE35322 [20] GSE7381 [6] GSE8790 [22] GSE42299 [8] GSE54678 [6] GSE6482 [9] GSE13227 [6] GSE4768 [18] GSE22005 [23] GSE52597 [7] GSE10290 [24] GSE42473 [15] GSE50789 [96] GSE34765 [6] GSE22006 [19] GSE52474 [154] GSE24695 [9] GSE17513 [12] GSE38754 [40] GSE45968 [6] GSE35044 [9] GSE11035 [6] GSE39984 [18] GSE17462 [8] GSE4238 [24] GSE51417 [60] GSE5296 [96] GSE25908 [111] GSE3100 [23] GSE36833 [49] GSE10589 [6] GSE21263 [68] GSE4411 [11] GSE24920 [19] GSE44363 [16] GSE11981 [8] GSE14395 [24] GSE20398 [30] GSE6487 [30] GSE24873 [48] GSE3822 [16] GSE1806 [22] GSE14710 [12] GSE32937 [8] GSE33931 [42] GSE50122 [10] GSE12499 [10] GSE40087 [15] CEM+ CEM GSE4671 [28] GSE19657 [21] GSE8044 [6] GSE43635 [9] GSE20604 [6] GSE17649 [36] 0.0 GSE27630 [8] GSE24512 [29]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 437.90 440.22 440.75 449.70 454.02 472.55 475.02 482.42 489.78 493.65 500.49 509.86 514.33 523.48 527.70 529.59 538.74 538.77 539.72 561.75 563.50 574.60 575.40 612.85 620.89 629.92 630.30 634.59 636.51 636.97 660.85 669.01 701.47 729.65 741.63 778.45 780.71 1.0 Notes 2310002L09Rik Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page2 Tmem182 Tmem38a Ppp1r27 Mybpc1 Cacng1 Cox7a1 Sh3bgr Pdlim7 Pdlim3 Adssl1 Trim63 Lmod2 Lmod3 Eef1a2 Obscn Myoz3 Hspb3 Hspb6 Cox8b Myoz2 Asb15 Scn4b Asb11 Klhl40 Tnnc1 Fabp3 Csrp3 Mylk4 Alpk3 Tnnt1 Jsrp1 Stac3 Fitm1 Txlnb Cap2 Asb2 Asb5 Pfkm Sgca Vgll2 Cav3 Murc Abra Myf6 Myl2 Rtn2 Mlf1 Des Hrc 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 217.37 220.49 222.51 228.96 232.88 238.63 239.24 241.29 242.76 250.48 252.51 254.34 254.40 255.44 257.51 262.30 263.35 266.86 274.12 277.34 284.81 286.51 287.14 289.90 291.56 292.27 294.33 298.73 300.59 309.74 311.74 318.32 319.15 327.15 331.89 350.12 363.50 390.06 391.78 397.20 398.40 405.65 405.87 408.42 415.88 420.70 421.96 424.24 424.96 437.74 1.0 Notes Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page3 Macrod1 Synpo2l Mapk12 Popdc3 Unc45b Dusp27 Dusp13 Myom3 Prkag3 Smtnl2 Tmod1 Mybph Slc2a4 Tceal7 Perm1 Hspb2 Myoz1 Hspb7 Capn3 Asb10 Adck3 Asb12 Klhl30 Phkg1 Asb14 Phka1 Tbx15 Coro6 Tcea3 Mef2c Mylk2 Ctxn3 Ddit4l Alpk2 Tnni1 Tpm3 Myh7 Myh8 Lrrc2 Xirp1 Hhatl Yipf7 Sgcg Nexn Fsd2 Pkia Flnc Fhl1 Mlip Agl 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 127.89 129.30 130.66 131.19 134.10 134.17 138.65 138.79 141.57 141.60 141.95 142.43 142.88 143.24 143.43 144.86 146.40 148.07 148.39 149.32 149.83 151.58 151.92 156.70 157.72 165.15 165.36 166.64 166.75 171.79 175.68 177.30 181.21 183.62 184.55 188.99 192.05 192.91 194.41 194.76 195.99 198.26 202.52 202.94 203.19 205.87 207.56 209.53 210.91 214.46 1.0 Notes Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page4 Cacna2d1 Ppp1r14c Slc25a12 Myadml2 Smarcd3 Ppapdc3 Tmem52 Ppp2r3a Pacsin3 Adprhl1 Coq10a Cacng6 Ptges3l Mustn1 Chrna1 Mettl22 Rbfox1 Atp1a2 Ptp4a3 Smco1 Lmcd1 Fem1a Myod1 Nmrk2 Mss51 Lrrc20 Rapsn Synpo Akap6 Acyp2 Kcna7 Casq2 Fxyd1 Ndrg2 Snta1 Synm Gmpr Mief2 Phtf2 Gys1 Neu2 Ank1 Pdk4 Bves Pitx2 Dtna Gyg Me3 Cfl2 Cilp 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 52.42 53.75 55.35 55.94 56.16 58.51 59.36 59.52 60.22 60.85 63.12 63.98 64.94 67.15 68.55 69.84 71.73 71.76 74.56 74.59 75.21 76.08 76.50 76.84 77.75 81.19 82.07 82.11 85.04 85.33 89.19 89.94 90.95 97.32 98.15 99.18 99.26 99.43 100.01 102.48 108.79 109.63 110.15 114.53 114.83 118.15 121.71 122.58 123.25 124.45 1.0 Notes Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page5 Ppp1r3c Popdc2 Tuba4a Atp1b4 Atp5g1 Prkab2 Rbm38 Aamdc Atp2a2 Pbxip1 Hspa1l Shisa4 Shisa2 Neurl2 Lrrc39 Hrasls Hspb8 Kcmf1 Usp13 Ubac1 Scn1b Vdac1 Scn4a Tuba8 Fndc5 Thbs4 Lynx1 Fyco1 Tacc2 Prkcq Stau2 Fgf13 Myog Myoc Ugp2 Coq9 Clip4 Phkb Aco2 Pdk2 Ybx3 Fbp2 Lbx1 Jph1 Mfn2 Car3 Six1 Tpi1 Art5 Egf 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 25.19 25.27 26.53 27.08 27.86 28.39 28.44 28.61 29.46 29.83 31.38 31.69 32.94 33.06 34.13 34.30 34.97 35.71 36.14 36.21 36.69 38.12 38.48 38.64 38.78 39.90 40.30 40.33 40.44 40.61 41.50 42.38 42.39 42.61 43.27 43.90 44.22 44.30 44.30 44.91 45.06 45.41 45.88 46.67 47.08 47.33 48.50 49.16 49.46 50.83 1.0 Notes 2410127L17Rik Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page6 AI464131 Fam213b Dennd4b Chchd10 Rps6ka2 Kbtbd13 Gm4980 Camk2b Pm20d2 Slc25a4 Ube2d1 Fbxo32 Arpp21 Cyb5r1 Ndufs7 Ndufs2 Rbm20 Dnajb5 Prkaa2 Kcnj12 Slc8a3 Lrrc38 Ube2b Hif1an Cand2 Pdha1 Acacb Abcc9 Reep1 Wfdc1 Tarsl2 Fxyd6 Dmpk Pink1 Idh3a Ipo13 Mdh2 Ip6k3 Myh3 Aqp4 Usp2 Ucp3 Plin4 Sync Itga7 Myl4 Mn1 Crat Hk2 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE28031 [6] Scale ofaveragePearsoncorrelations GSE51927 [59] GSE9743 [12] GSE13421 [8] GSE29685 [132] GSE49128 [17] GSE37975 [8] 0.2 GSE9400 [8] GSE42049 [8] GSE22989 [10] GSE31570 [6] GSE40261 [8] GSE11804 [12] GSE33770 [8] GSE10813 [12] GSE55733 [24] 0.4 GSE10192 [24] GSE17797 [19] GSE19668 [50] GSE30138 [51] GSE7302 [6] GSE18993 [13] GSE20325 [6] GSE27987 [31] GSE8349 [10] 0.6 GSE13103 [8] GSE25911 [26] GSE8660 [6] GSE42008 [6] GSE19925 [6] GSE30192 [6] GSE27675 [14] GSE12948 [9] GSE43899 [12] 0.8 GSE8025 [21] GSE8407 [17] GSE17709 [18] GSE5891 [6] Score 5.33 5.41 5.47 5.75 6.56 7.05 7.11 7.16 7.91 8.52 8.57 8.63 8.97 9.13 10.21 10.27 10.71 10.86 11.05 12.13 12.19 12.39 13.01 13.51 13.54 13.54 13.87 15.10 16.01 16.01 16.83 17.28 17.72 18.17 18.44 18.50 18.74 18.77 18.92 19.05 19.22 19.54 20.33 20.50 20.83 20.83 21.21 22.23 23.27 25.01 1.0 Notes 2310022A10Rik Symbol Num ofCEMGenes:13.Predicted300.SelectedDatasets:158.Strength:15.7 CEM 1,Geneset"[G]Iband",Page7 Mettl11b Ppp1r1a Ehbp1l1 Chrnb1 Ndufs3 Cdh13 Lrtm1 Park7 Idh3g Myh1 Sim2 Ldha 0.0 1.0

GSE20152 [8] GSE22506 [12]

GSE6210 [12] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE31431 [34] GSE41759 [14] GSE12730 [24] GSE20577 [12] GSE41997 [6] GSE50813 [24] GSE24243 [6] GSE49122 [14] GSE11990 [20] GSE32316 [12] GSE24207 [73] GSE38257 [14] GSE51628 [15] GSE4786 [9] GSE13563 [6] GSE25295 [25] GSE32422 [6] GSE19616 [16] GSE4866 [10] GSE27309 [10] GSE9954 [70] GSE52358 [8] GSE12248 [83] GSE22307 [23] GSE28389 [20] GSE19079 [6] GSE16992 [48] GSE6055 [8] GSE41342 [26] GSE5800 [6] GSE36826 [12] GSE19517 [6] GSE10246 [182] GSE3501 [6] GSE31004 [8] GSE43242 [10] GSE11186 [33] GSE12993 [6] GSE15772 [8] GSE51883 [30] GSE7863 [16] GSE16377 [6] GSE30688 [9] GSE17739 [24] GSE5657 [20] GSE17825 [18] GSE9330 [8] GSE8498 [6] GSE41907 [7] GSE13224 [6] GSE46209 [21] GSE31561 [36] GSE21716 [28] GSE39897 [36] GSE28457 [24] GSE43373 [130] GSE33308 [10] GSE16110 [16] GSE5861 [6] GSE38822 [22] GSE8733 [24] GSE18567 [24] GSE51686 [9] GSE37191 [12] GSE38048 [20] GSE30865 [68] GSE43779 [6] GSE16777 [38] GSE16496 [102] GSE13071 [15] GSE56236 [12] GSE28417 [12] GSE11343 [19] GSE13032 [18] GSE35357 [12] GSE20726 [9] GSE4694 [6] GSE9368 [12] GSE11291 [60] GSE23006 [48] GSE15155 [12] GSE6591 [15] GSE23724 [8] GSE27628 [34] GSE59437 [30] GSE23782 [18] GSE7694 [12] GSE7475 [16] GSE9725 [16] GSE32020 [26] GSE21247 [60] GSE6686 [13] GSE38693 [8] GSE8513 [10] GSE3313 [24] GSE43381 [26] GSE19204 [6] GSE9460 [26] GSE19793 [32] GSE6837 [8] GSE35206 [14] GSE5313 [6] GSE18341 [30] GSE35322 [20] GSE7381 [6] GSE8790 [22] GSE42299 [8] GSE54678 [6] GSE6482 [9] GSE13227 [6] GSE4768 [18] GSE22005 [23] GSE52597 [7] GSE10290 [24] GSE42473 [15] GSE50789 [96] GSE34765 [6] GSE22006 [19] GSE52474 [154] GSE24695 [9] GSE17513 [12] GSE38754 [40] GSE45968 [6] GSE35044 [9] GSE11035 [6] GSE39984 [18] GSE17462 [8] GSE4238 [24] GSE51417 [60] GSE5296 [96] GSE25908 [111] GSE3100 [23] GSE36833 [49] GSE10589 [6] GSE21263 [68] GSE4411 [11] GSE24920 [19] GSE44363 [16] GSE11981 [8] GSE14395 [24] GSE20398 [30] GSE6487 [30] GSE24873 [48] GSE3822 [16] GSE1806 [22] GSE14710 [12] GSE32937 [8] GSE33931 [42] GSE50122 [10] GSE12499 [10] GSE40087 [15] CEM+ CEM GSE4671 [28] GSE19657 [21] GSE8044 [6] GSE43635 [9] GSE20604 [6] GSE17649 [36] 0.0 GSE27630 [8] GSE24512 [29]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20152 Status: Public on Jan 15 2011 Title: The role of SphK1 in hTNFÎ± induced inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20644167 Summary & Design: Summary: The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity.

SphK1 is a sphingolipid enzyme that converts sphingosine to bioactive sphingosine-1-phosphate (S1P). Recent data suggest a potential relationship between SphK1 and TNFÎ± and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNFÎ± and SphK1 using an in vivo model. Transgenic hTNFÎ± mice, which develop a spontaneous arthritis (limited to paws) at 20 weeks, were crossed with SphK1 activity null mice (SphK1-/-) to study the development of inflammatory arthritis in the functional absence of SphK1. Results show that hTNF/SphK1-/- have significantly less severity and progression of arthritis and bone erosions as measured through micro-CT images. Additionally, less COX-2 protein, mTNFÎ± transcript levels and fewer Th 17 cells were detected in the joints of hTNF/SphK1-/- compared to hTNF/SphK1+/+ mice. Microarray analysis of the ankle joint showed that hTNF/SphK1-/- mice have increased transcript levels of IL-6 and SOCS3 compared to hTNF/SphK1+/+ mice. Finally, fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1-/- mice compared to hTNF/SphK1+/+ mice. These data show that SphK1 plays a role in hTNFÎ± induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3.

Overall design: Two wild-type replicates; three replicates of human TNFa transgene overexpression and normal sphingosine kinase 1; three replicates of human TNFa transgene overexpression and sphingosine kinase 1 null.

Background corr dist: KL-Divergence = 0.0305, L1-Distance = 0.0370, L2-Distance = 0.0018, Normal std = 0.6871

0.616 Kernel fit Pairwise Correlations Normal fit

Density 0.308

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

Ankle-hTNFaAnkle-hTNFa overexpressionAnkle-Sphk1 overexpressionAnkle-hTNFa norm-1 andAnkle-Sphk1 SphK1 overexpression(0.378723) andAnkle-hTNFa null-1SphK1 norm-2Ankle-hTNFa (0.0335456) null-2 overexpression(0.324837) andAnkle-hTNFa (0.0799818) SphK1 overexpression null-3 overexpression and (0.0641912) Sphk1 and norm-1Sphk1 and[ min norm-2(0.0289251)Sphk1 norm-3(0.0391663)] (0.0506297)[ medium ] [ max ] CEM 1 Atp2a1 19751.0 22100.1 32614.0 P ( S | Z, I ) = 1.00 Ryr1 3190.7 6279.2 18219.6 Mean Corr = 0.94858 Casq1 4703.9 6833.0 16649.7 Tcap 4639.1 9464.4 26126.1 Mypn 955.2 2132.5 7247.2 Cacna1s 613.0 1158.7 4020.6 Ttn 222.8 525.8 1955.3 Ankrd23 1530.3 2421.6 8664.0 Smtnl1 354.5 830.8 4650.6 Aldoa 20328.5 22666.9 30169.8 Actc1 263.1 355.0 957.6 Myl3 637.5 849.0 7594.9 Ankrd2 353.1 557.1 3042.0 Tnnt3 7588.7 12575.2 25236.2 Tnni2 8838.8 15375.0 30854.8 Tnnc2 19479.1 25325.4 33299.3 Myot 2271.8 4119.6 12972.8 Mylpf 7641.5 11412.3 24336.2 CEM 1 + Myl1 14762.4 20570.6 29393.4 Top 10 Genes Ckm 9605.4 13794.1 28788.5 Acta1 21315.8 26218.5 38516.9 Mybpc2 1664.9 2699.2 11274.8 Ldb3 1721.7 3195.4 10249.1

Null module Ankrd1 Kat2b GEO Series "GSE22506" 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=GSE22506 Status: Public on Jun 26 2010 Title: Unacylated Ghrelin Rapidly Modulates Lipogenic and Insulin Signaling Pathway Gene Expression in Metabolically Active Tissues of GHSR Deleted Mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20668691 Summary & Design: Summary: Background: There is increasing evidence that unacylated ghrelin (UAG) improves insulin sensitivity and glucose homeostasis; however, the mechanism for this activity is not fully understood since a UAG receptor has not been discovered. Methodology/Principal Findings: To assess potential mechanisms of UAG action in vivo, we examined rapid effects of UAG on genome-wide expression patterns in fat, muscle and liver of growth hormone secretagogue receptor (GHSR)-ablated mice using microarrays. Expression data were analyzed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis. Regulation of subsets of these genes was verified by quantitative PCR in an independent experiment. UAG acutely regulated clusters of genes involved in glucose and lipid metabolism in all three tissues, consistent with enhancement of insulin sensitivity. Conclusions/Significance: Fat, muscle and liver are central to the control of lipid and glucose homeostasis. UAG rapidly modulates the expression of metabolically important genes in these tissues in GHSR-deleted mice indicating a direct, GHSR-independent, action of UAG to improve insulin sensitivity and metabolic profile.

Overall design: White adipose tissue (gonadal), muscle and liver collected from female GHSR knockout mice 6 hours after ip. injection with saline or unacylated ghrelin (20 nmol/kg). Two replicates.

Background corr dist: KL-Divergence = 0.0581, L1-Distance = 0.0487, L2-Distance = 0.0038, Normal std = 0.5847

0.731 Kernel fit Pairwise Correlations Normal fit

Density 0.365

0.000 CEM 1

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

Pre-normalization Quantiles

White adipose,White adipose, Whitemouse adipose, Whiteinjectedmouse adipose, Muscle,injectedmouse ip. with Muscle, injectedmousemouse ip.saline with Muscle, injectedinjectedmouse 1 ip.saline (0.0356463) withMuscle, injectedmouse 2 ip.ip.UAG (0.0480922) withwith 1Liver, injectedmouse (0.0464628) ip.UAGsaline with mouse 2Liver, injected 1(0.0391959) ip.saline (0.172973) with injectedmouseLiver, 2 ip.UAG (0.110145) with injectedmouse ip.Liver,1 (0.200535) UAGwith injectedmouse ip.2saline (0.15014) with injected 1 ip.saline (0.0449472) with 2 ip.UAG (0.0578278) with 1 (0.0453327)[UAG min 2 (0.0487019) ] [ medium ] [ max ] CEM 1 Atp2a1 60.8 204.0 44718.9 P ( S | Z, I ) = 1.00 Ryr1 9.6 123.6 26675.9 Mean Corr = 0.92630 Casq1 30.4 133.6 30611.6 Tcap 97.5 167.7 32938.9 Mypn 12.0 70.0 7348.2 Cacna1s 18.7 69.0 6793.8 Ttn 8.7 24.6 2565.0 Ankrd23 16.0 110.6 21527.8 Smtnl1 13.7 32.6 2722.3 Aldoa 1622.0 17810.6 46910.3 Actc1 29.4 153.9 22063.0 Myl3 29.3 243.0 7701.4 Ankrd2 25.3 234.2 6506.7 Tnnt3 27.4 118.9 60114.0 Tnni2 16.2 72.3 58036.7 Tnnc2 11.2 110.4 36792.8 Myot 11.7 58.9 36024.4 Mylpf 72.9 156.8 53422.9 CEM 1 + Myl1 14.7 2759.8 46981.1 Top 10 Genes Ckm 15.8 448.9 47383.5 Acta1 24.2 4555.0 44298.9 Mybpc2 18.5 133.8 37351.6 Ldb3 15.0 43.8 27052.1

Null module Ankrd1 Kat2b GEO Series "GSE6210" 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=GSE6210 Status: Public on Jan 01 2007 Title: Hypomorphic Mutation in PGC1beta causes mitochondrial dysfunction and liver insulin resistance Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17141629 Summary & Design: Summary: PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver.

Keywords: Liver and quadricpes muscle gene expression, WT vs. PGC1beta mutant

Overall design: Gene expression levels in liver tissue and quadriceps muscle were compared between WT/Control and PGC1beta mutant tissue. Total RNA was extracted from liver and skeletal muscle using RNAeasy kit (Qiagen, Valencia, CA), according to the manufacturers instructions. Synthesis of cRNA, hybridization and scanning of the Affymetrix Murine 430 2.0 chip was performed by Dana Farber Cancer Institute Microarray Core Facility. The microarray data was analyzed by Clustering Analysis using the d-Chip software (Li and Wong, 2001).

Background corr dist: KL-Divergence = 0.0507, L1-Distance = 0.0691, L2-Distance = 0.0068, Normal std = 0.6428

0.709 Kernel fit Pairwise Correlations Normal fit

Density 0.354

0.000 CEM 1

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

Pre-normalization Quantiles

Liver ExperimentLiver ControlLiver 3 (0.0829614) Control 2 Liver(0.0799975) Experiment 3 Liver(0.0903569) ExperimentLiver 1 (0.0741455) ControlMuscle 2 (0.0798365) 1 MuscleControl(0.0878508) MuscleControl 1 (0.0680485) MuscleControl 2 (0.0875563) MuscleExperiment 3 (0.091842) MuscleExperiment 1 (0.0790381) Experiment 2 (0.114376) 3 (0.0639909)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 59.0 74438.3 84042.4 P ( S | Z, I ) = 1.00 Ryr1 12.0 49601.1 58443.9 Mean Corr = 0.92078 Casq1 403.2 44051.7 50425.2 Tcap 134.3 44016.7 52383.8 Mypn 6.5 14276.7 18100.6 Cacna1s 17.8 8881.6 13452.0 Ttn 3.4 5174.0 6811.1 Ankrd23 35.6 18952.8 32501.1 Smtnl1 7.5 258.7 672.2 Aldoa 2720.9 71308.4 81256.0 Actc1 19.7 50091.9 63442.3 Myl3 36.5 164.9 323.6 Ankrd2 9.5 294.3 1072.1 Tnnt3 13.1 69932.2 79018.1 Tnni2 12.3 72613.8 83003.6 Tnnc2 10.7 57572.4 64208.4 Myot 5.3 27795.9 32820.3 Mylpf 73.8 77731.6 89223.5 CEM 1 + Myl1 9.9 55179.4 61448.9 Top 10 Genes Ckm 34.6 67455.2 78499.3 Acta1 15.4 67018.1 76386.7 Mybpc2 6.8 58598.3 67617.6 Ldb3 8.9 46102.9 53768.9

Null module Ankrd1 Kat2b GEO Series "GSE31431" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 34 -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=GSE31431 Status: Public on Oct 03 2012 Title: Serial gene expression profiling in the liver of Pdgf-c Tg mice that developed hepatic fibrosis and tumors Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22651928 Summary & Design: Summary: Over expression of PDGF-C in mouse liver resulted in the progression of hepatic fibrosis, steatosis and the development of HCC; this mouse model closely resembles the human HCC that is frequently associated with hepatic fibrosis.

Peretinoin (generic name; code, NIK-333), developed by the Kowa Company, (Tokyo, Japan), is an oral acyclic retinoid (ACR) with a vitamin A-like structure that targets the retinoid nuclear receptor. Peretinoin effectively inhibits the progression of hepatic fibrosis and tumors in Pdgf-c Tg mice. Gene expression profiling was evaluated during the progression of hepatic fibrosis and tumors.

Overall design: After weaning at week 4, Pdgf-c Tg or non-transgenic WT mice were fed a basal diet or a diet containing+0.06% peretinoin respectively. At week 20, mice were sacrificed for the analysis of progression of hepatic fibrosis. At week 48, mice were sacrificed for the analysis of the development of hepatic tumors.

Background corr dist: KL-Divergence = 0.3939, L1-Distance = 0.0727, L2-Distance = 0.0157, Normal std = 0.2498

1.597 Kernel fit Pairwise Correlations Normal fit

Density 0.799

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

20w WT-120w (0.00319739) WT-220w (0.0070348) WT-320w (0.00758578) WT-420w (0.00512944) WT-548w (0.00718922) WT-148w (0.0175691) WT-248w (0.00353403) WT-348w (0.00589519) WT-420w (0.0166395) PDGFC-120w PDGFC-2 (0.00503438)20w PDGFC-3 (0.0059625)20w PDGFC-4 (0.0114748)20w PDGFC-5 (0.00307277)48w PDGFC-1 (0.00324011)48w PDGFC-2 (0.0159149)48w PDGFC-3 (0.00801594)48w PDGFC-4 (0.00545755)48w PDGFC-5 (0.394342)48w PDGFC (0.00473223)48w PDGFCtumor-148w PDGFCtumor-2 (0.0140789)48w PDGFCtumor-3 (0.00528066)48w PDGFCtumor-4 (0.00550547)20w PDGFC+0.06%tumor-5 (0.00576365)20w PDGFC+0.06% (0.00651014)20w PDGFC+0.06%peretinoin-120w PDGFC+0.06%peretinoin-220w (0.0114563) PDGFC+0.06%peretinoin-348w (0.00903146) PDGFC+0.06%peretinoin-448w (0.00609281) PDGFC+0.06%peretinoin-548w (0.0051802) PDGFC+0.06%peretinoin-148w (0.0726223) PDGFC+0.06%peretinoin-248w (0.308236) PDGFC+0.06%peretinoin-3 (0.00456464) peretinoin-4 (0.00650169) peretinoin-5 (0.00436789)[ (0.00378711)min ] [ medium ] [ max ] CEM 1 Atp2a1 54.8 101.5 10749.9 P ( S | Z, I ) = 1.00 Ryr1 2.2 21.2 1996.3 Mean Corr = 0.91461 Casq1 11.0 90.3 2051.8 Tcap 45.2 83.8 6125.6 Mypn 3.0 11.4 461.6 Cacna1s 2.5 9.5 632.6 Ttn 1.0 9.5 227.2 Ankrd23 7.2 48.5 3107.6 Smtnl1 4.4 27.3 560.5 Aldoa 1315.8 3104.6 10560.2 Actc1 10.3 78.3 809.3 Myl3 11.8 78.4 1728.9 Ankrd2 4.3 57.9 775.1 Tnnt3 2.2 23.3 15933.0 Tnni2 2.3 8.5 17843.6 Tnnc2 2.1 7.2 19740.1 Myot 1.0 15.4 7433.1 Mylpf 73.8 114.3 12820.2 CEM 1 + Myl1 3.7 41.0 17375.8 Top 10 Genes Ckm 16.9 68.1 18179.3 Acta1 9.5 75.5 25087.1 Mybpc2 2.1 28.3 1798.1 Ldb3 3.2 8.8 2605.5

Null module Ankrd1 Kat2b GEO Series "GSE41759" 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=GSE41759 Status: Public on Apr 19 2013 Title: Differential Gene Expression and Mitochondrial Dysfunction in Imprinting center deletion (PWS- IC del) Mouse model of Prader-Willi Syndrome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Prader-Willi syndrome (PWS) is a genetic disorder caused by deficiency of imprinted gene expression from the paternal chromosome 15q11-15q13 and clinically characterized by neonatal hypotonia, short stature, cognitive impairment, hypogonadism, hyperphagia, morbid obesity and diabetes. Previous clinical studies suggest that a defect in energy metabolism may be involved in the pathogenesis of PWS. Assessment of enzyme activities of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the brain, heart, liver and muscle were assessed.

We used microarrays to detail the global programme of gene expression underlyingthe PWS and identified distinct classes of disregulated genes during this process.

Overall design: Skeletal (quadriceps) muscle Vastus Lateralis and whole brain samples from the mutant mice and their wild-type age-matched littermates were analyzed by microarray technology using the Mouse Genome 430 2.0 arrays (Affymetrix).

Background corr dist: KL-Divergence = 0.0080, L1-Distance = 0.0325, L2-Distance = 0.0010, Normal std = 0.9775

0.408 Kernel fit Pairwise Correlations Normal fit

Density 0.204

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

muscle brainVastus tissue muscleLateralis, sample, brainVastus wild tissuewild muscletypeLateralis, type sample,mice, brainVastusmice, wild biological tissuewild biological muscletypeLateralis, type sample,mice, replica brainVastusmice, replica wild biological tissue wild1biological muscletypeLateralis,(0.102542) 1 type (0.0646657) sample,mice, replica brainVastusmice, replica wild biological tissue wild2biological muscletypeLateralis,(0.0454002) 2 type (0.0645066) sample,mice, replica brainVastusmice, replica mutant biological tissue mutant3biological muscleLateralis,(0.0882681) 3 mice, (0.0630854) sample, mice,replica brainVastus biological replica mutant biological tissue mutant4 Lateralis,(0.113085) 4 mice, (0.0631929) replicasample, mice, replica biological mutant 1biological mutant(0.0722632) 1 (0.0640446) mice, replica mice, replica[ biological min 2biological (0.0636317) 2 (0.0641083) replica] replica 3 (0.0674953) 3 (0.0637113)[ medium ] [ max ] CEM 1 Atp2a1 34.4 20931.1 23502.9 P ( S | Z, I ) = 1.00 Ryr1 48.7 16665.8 20271.1 Mean Corr = 0.90817 Casq1 169.7 15725.8 18738.5 Tcap 78.3 14788.2 19002.6 Mypn 85.2 10843.2 11708.2 Cacna1s 6.8 8393.2 9355.0 Ttn 2.7 4286.3 6079.8 Ankrd23 55.7 15623.4 19335.6 Smtnl1 16.1 1515.5 3279.8 Aldoa 8486.2 21460.7 24819.2 Actc1 220.0 8559.3 19848.8 Myl3 188.4 2156.8 8930.6 Ankrd2 56.4 461.6 2876.8 Tnnt3 14.0 30883.3 32450.3 Tnni2 16.0 25910.4 28224.0 Tnnc2 26.3 18039.3 20013.9 Myot 17.7 21561.3 23650.8 Mylpf 29.3 23775.1 25595.1 CEM 1 + Myl1 96.9 19970.1 24970.8 Top 10 Genes Ckm 65.3 21011.0 23991.8 Acta1 397.2 19385.9 24389.3 Mybpc2 1.9 23805.3 25132.8 Ldb3 65.4 17338.1 18787.3

Null module Ankrd1 Kat2b GEO Series "GSE12730" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12730 Status: Public on Nov 07 2009 Title: Mouse gestational protein restriction: Newborn offspring liver and hindleg muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19823102 Summary & Design: Summary: Gestational protein restriction is a model for low birth size. We hypothesized that taurine supplementation would protect against changes in newborn liver and muscle caused by a maternal low protein diet.

Overall design: The liver and muscle samples were normalized separately.

Background corr dist: KL-Divergence = 0.0311, L1-Distance = 0.0319, L2-Distance = 0.0015, Normal std = 0.6489

0.615 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

MaternalMaternal normalMaternal normalproteinMaternal normalproteinoffspringMaternal normalproteinoffspring liver,Maternal normalprotein offspringbiological liver,Maternal normalprotein +biological 1%liver, replicate Maternaltaurine lowprotein +biological 1% replicateprotein 1Maternaltaurineoffspring (0.0345332) low+ 1% replicateproteinoffspring 2Maternaltaurineoffspring (0.0339442)low liver, proteinoffspring 3Maternal offspringbiologicalliver, (0.0360244)low liver, protein offspringbiologicalMaternal biologicalliver, low liver, replicate protein +biological Maternal 1%biologicalliver, lowreplicate replicatetaurine 1protein +biological (0.0348165) Maternal1% normalreplicate replicate1taurineoffspring 2(0.0340318) + (0.0308937) Maternal1% normalproteinreplicate 2taurineoffspring 3(0.0319032) liver, (0.0355753)Maternal normalproteinoffspring 3 offspringbiological (0.035844) liver,Maternal normalproteinoffspring muscle,biological liver, Maternalreplicate normalproteinoffspring muscle,biological biological Maternalreplicate normalprotein1+ (0.0396541) 1%muscle, biological Maternalreplicatetaurine replicate lowprotein2+ (0.0349061)1% biologicalprotein Maternaltaurineoffspring replicate low3 +1 (0.0336049) 1%(0.0777778) proteinoffspring Maternaltaurineoffspring replicate low muscle,2 (0.0597251) proteinoffspring Maternaloffspring muscle, low muscle,3 biological (0.0537645) proteinoffspringMaternal muscle, lowbiological muscle, biological protein +replicate 1%muscle, lowbiological biologicaltaurine replicate protein +replicate 1%1 biological (0.104342) taurineoffspring replicate +replicate1 1%2(0.0070407) (0.0405398) taurineoffspring replicate muscle,2[ 3(0.0331017) (0.0386884)min offspring muscle,3 biological (0.0282717) ] muscle, biological replicate biological [replicate 1medium (0.0311747) replicate 2 (0.049578) 3 (0.0602647) ] [ max ] CEM 1 Atp2a1 83.6 20078.2 39072.9 P ( S | Z, I ) = 1.00 Ryr1 52.9 2896.4 11296.5 Mean Corr = 0.89060 Casq1 91.7 4992.3 19154.5 Tcap 101.3 2314.5 7249.1 Mypn 54.2 2620.3 8592.2 Cacna1s 43.0 835.8 2121.2 Ttn 41.9 1369.0 4916.5 Ankrd23 128.2 257.9 1744.3 Smtnl1 90.7 719.9 3610.1 Aldoa 3800.1 28505.4 47793.4 Actc1 117.6 57182.7 84588.2 Myl3 114.5 2515.1 5470.6 Ankrd2 90.3 296.4 3058.7 Tnnt3 58.6 28819.9 58559.4 Tnni2 61.5 34139.9 66232.2 Tnnc2 88.2 51547.8 84797.9 Myot 38.3 6938.8 22059.2 Mylpf 136.3 59140.4 98906.7 CEM 1 + Myl1 57.0 62952.5 93807.6 Top 10 Genes Ckm 133.9 35311.5 67117.8 Acta1 171.9 76439.8 116660.5 Mybpc2 73.9 197.0 7047.9 Ldb3 73.6 5470.6 17937.5

Null module Ankrd1 Kat2b GEO Series "GSE20577" 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=GSE20577 Status: Public on Dec 01 2010 Title: Gestational taurine supplementation of mice: effect on offspring gene expression in liver and skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Taurine is known to be important for fetal well being and to be able to prevent effects of a low birthweight phenotype when supplemented to pregnant dams.

We hypothesized that gestational taurine supplementation would affect gene expression level in 4w offspring liver and skeletal muscle.

Overall design: Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed at 4 weeks of age and liver and quadriceps skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau). The liver and muscle samples were normalized separately.

Background corr dist: KL-Divergence = 0.0243, L1-Distance = 0.0507, L2-Distance = 0.0039, Normal std = 0.7351

0.543 Kernel fit Pairwise Correlations Normal fit

Density 0.271

0.000 CEM 1

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

Pre-normalization Quantiles

4 week 4liver, week untreated, 4liver, week untreated, 4liver, biologicalweek untreated, 4liver, biologicalweek replicate in 4liver,utero biologicalweek replicate in 1taurine 4liver,(0.0645012)utero week replicate in 2taurinesupplementation, 4skeletal(0.0643221)utero week 3taurinesupplementation, 4skeletal (0.0652943)muscle, week supplementation, 4skeletal muscle, weekuntreated,biological 4skeletal muscle, weekuntreated,biological biologicalreplicate 4skeletal muscle, weekuntreated,biological biologicalreplicate 1skeletal replicate muscle, (0.064455)in utero biologicalreplicate 2 replicate muscle, (0.0697834)in 1taurine (0.15997)utero 3 replicate (0.0650955)in 2taurinesupplementation, (0.0787919)utero[ 3taurineminsupplementation, (0.0937716) supplementation, ] biological biological replicate[ mediumbiological replicate 1 (0.123857) replicate 2 (0.0875714) ] 3 (0.062586)[ max ] CEM 1 Atp2a1 140.6 84999.7 96156.1 P ( S | Z, I ) = 1.00 Ryr1 66.8 35146.2 39652.2 Mean Corr = 0.87227 Casq1 60.8 23672.8 53157.6 Tcap 119.9 24461.4 50038.4 Mypn 63.8 10415.0 16158.8 Cacna1s 52.8 6393.5 9614.5 Ttn 52.4 2210.6 5150.2 Ankrd23 141.9 13360.3 40352.3 Smtnl1 96.5 2541.2 4564.2 Aldoa 2845.1 82720.6 90220.6 Actc1 62.2 3424.5 61070.7 Myl3 135.9 6418.2 20951.9 Ankrd2 96.8 4062.8 25938.9 Tnnt3 51.5 76435.6 84968.3 Tnni2 60.7 87600.7 97850.0 Tnnc2 61.5 81175.2 96117.6 Myot 50.0 31679.6 45693.2 Mylpf 104.2 94413.7 107998.7 CEM 1 + Myl1 66.3 88149.4 101285.5 Top 10 Genes Ckm 97.5 86180.4 101527.4 Acta1 112.2 105300.1 120935.9 Mybpc2 70.9 44352.9 68477.7 Ldb3 85.4 22904.2 40474.2

Null module Ankrd1 Kat2b GEO Series "GSE41997" 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=GSE41997 Status: Public on Dec 12 2013 Title: Expression data from Dmp1-GFP sorted osteocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24333171 Summary & Design: Summary: Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/Î²-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER˛– deletion mice (ER˛–˛Ocy/˛Ocy) were generated by mating ER˛– floxed mice with Dmp1-Cre mice to determine functions of ERÎ± in osteocytes. Trabecular bone mineral density of female, but not male ER˛–˛Ocy/˛Ocy mice was significantly decreased. Bone formation parameters in ER˛–˛Ocy/˛Ocy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERÎ± in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER˛–, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ER˛–˛Ocy/˛Ocy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or Î²-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERÎ± in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.

Overall design: Wild type and osteocyte-specific Estrogen Receptor alpha knock-out mice were generated. The number of both genotypes of mice was three. Calvarial osteocytes of both genotypes harboring Dmp1-GFP were extracted by sequential enzymatic digestion, followed by FACS Aria sorting and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling.

Background corr dist: KL-Divergence = 0.0479, L1-Distance = 0.0228, L2-Distance = 0.0006, Normal std = 0.5831

0.702 Kernel fit Pairwise Correlations Normal fit

Density 0.351

0.000 CEM 1

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

Pre-normalization Quantiles

Osteocyte_WT,Osteocyte_WT,Osteocyte_WT, biologicalOsteocyte_ERaKO, biological rep1Osteocyte_ERaKO, biological(0.320433) rep2Osteocyte_ERaKO, (0.234382) rep3 biological (0.215423) biological rep1 biological(0.104728) rep2 (0.0816351) [rep3 min (0.0433977) ] [ medium ] [ max ] CEM 1 Atp2a1 16.8 226.3 552.9 P ( S | Z, I ) = 1.00 Ryr1 6.6 86.4 129.6 Mean Corr = 0.86170 Casq1 57.4 279.7 1031.2 Tcap 55.9 598.0 1257.0 Mypn 5.1 97.2 212.3 Cacna1s 8.2 54.2 148.5 Ttn 41.6 81.6 104.7 Ankrd23 26.4 214.3 723.3 Smtnl1 5.6 137.6 316.0 Aldoa 7239.6 11230.3 16506.5 Actc1 171.2 2277.1 5122.6 Myl3 80.0 241.9 444.9 Ankrd2 13.2 126.6 215.5 Tnnt3 55.9 4218.9 10666.6 Tnni2 8.1 6824.8 14186.4 Tnnc2 91.4 12182.4 26003.1 Myot 29.5 678.8 2276.5 Mylpf 102.1 18129.1 34770.8 CEM 1 + Myl1 210.3 21498.7 43258.7 Top 10 Genes Ckm 19.8 2736.0 8533.7 Acta1 126.0 13638.4 34696.8 Mybpc2 5.0 105.8 602.5 Ldb3 13.2 364.6 913.7

Null module Ankrd1 Kat2b GEO Series "GSE50813" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50813 Status: Public on Dec 31 2013 Title: Prevention of mammary tumor progression by silencing HoxA1 via intraductal injection of nanoparticle-formulated siRNA Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24382894 Summary & Design: Summary: Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.

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

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

0.911 Kernel fit Pairwise Correlations Normal fit

Density 0.455

0.000 CEM 1

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

Pre-normalization Quantiles

8 weeks8 wildweeks type8 wildweeks Mammary33 type8 wildweeks Mammary34 type8 wild(0.0186928)weeks Mammary35 type8 wild(0.00572639)weeks Mammary36 type8 tumor(0.210198)weeks Mammary37 8Mammary1 tumor(0.0389635)weeks 8Mammary2 tumor(0.0106715)weeks (0.185256) 8Mammary3 tumorweeks (0.0179687) 12Mammary4 tumor weeks (0.0103997) 12Mammary5 tumorweeks (0.0122539)12 Mammary6 tumorweeks (0.0154876)12 Mammary7 tumorweeks (0.00892184)12 Mammary8 tumorweeks (0.00626965)16 Mammary9 tumorweeks (0.0459751)16 Mammary10 tumorweeks (0.00413979)16 Mammary11 tumorweeks (0.0166311)16 Mammary13 tumorweeks (0.00900494)16 Mammary14 tumorweeks (0.0224781)20 Mammary15 tumorweeks (0.0340443)20 Mammary32 tumorweeks (0.120114)20 Mammary22 tumorweeks (0.0203301)20 Mammary23 tumorweeks (0.0303744) Mammary24 tumor (0.0536188) Mammary31 (0.054936) (0.047544)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 77.0 8228.5 28539.8 P ( S | Z, I ) = 1.00 Ryr1 38.2 2067.1 10244.7 Mean Corr = 0.83326 Casq1 60.1 2980.5 14109.6 Tcap 152.4 2726.7 12952.9 Mypn 21.1 454.4 2380.4 Cacna1s 22.9 382.4 1523.0 Ttn 28.6 197.6 972.2 Ankrd23 113.4 1054.8 5968.6 Smtnl1 48.8 290.2 1355.3 Aldoa 8059.0 27854.3 44044.9 Actc1 30.1 66.5 355.0 Myl3 75.5 108.2 329.1 Ankrd2 85.7 148.1 636.3 Tnnt3 45.0 13048.7 39794.7 Tnni2 180.7 14008.8 40002.1 Tnnc2 104.3 29480.7 55696.0 Myot 24.6 2107.6 10403.5 Mylpf 87.6 16942.1 40644.9 CEM 1 + Myl1 104.9 25674.1 51668.1 Top 10 Genes Ckm 75.6 15779.0 45797.7 Acta1 109.2 33168.4 63615.3 Mybpc2 46.8 4973.8 21970.6 Ldb3 57.2 1651.4 8950.0

Null module Ankrd1 Kat2b GEO Series "GSE24243" 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=GSE24243 Status: Public on May 09 2011 Title: Murine skin gene expression analysis of skin-specific Scd1-deficient and control mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21573029 Summary & Design: Summary: To help elucidate the metabolic changes in the skin that contribute to the obesity resistance and skin pathology in mice lacking Scd1, we performed microarray analysis of skin gene expression in male skin Scd1 knockout (SKO) and Scd1 flox/flox control (Lox) mice fed a standard rodent diet.

We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebocyte atrophy, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXRÎ±. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly, we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin pathology.

Overall design: We analyzed dorsal skin gene expression in non-fasted 8-9 week old male skin Scd1 knockout (SKO) mice (n=3) and Scd1flox/flox (Lox) control mice (n=3)on a C57BL/6J background using Affymetrix 430 2.0 microarrays.

Background corr dist: KL-Divergence = 0.0198, L1-Distance = 0.0107, L2-Distance = 0.0001, Normal std = 0.7416

0.538 Kernel fit Pairwise Correlations Normal fit

Density 0.269

0.000 CEM 1

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

Pre-normalization Quantiles

Skin_Lox_Control_Rep1Skin_Lox_Control_Rep2Skin_Lox_Control_Rep3Skin_SKO_Rep1 (0.170595)Skin_SKO_Rep2 (0.194397)Skin_SKO_Rep3 (0.238309)(0.16367) (0.141357) (0.0916722) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 4232.6 16775.1 21027.0 P ( S | Z, I ) = 1.00 Ryr1 1568.7 7771.8 8569.7 Mean Corr = 0.83084 Casq1 1904.7 11722.8 13748.2 Tcap 6257.3 24594.1 28487.3 Mypn 630.0 3196.0 4305.5 Cacna1s 217.4 1228.8 1759.5 Ttn 48.7 562.2 621.6 Ankrd23 1074.4 2659.7 4014.6 Smtnl1 177.3 674.2 732.7 Aldoa 28970.9 42880.2 45199.8 Actc1 141.1 234.3 1034.7 Myl3 160.2 195.8 205.7 Ankrd2 293.3 807.3 1312.4 Tnnt3 3571.5 16903.4 19551.9 Tnni2 8342.8 38219.6 41074.5 Tnnc2 16319.6 42405.3 44763.1 Myot 160.8 1024.7 1504.5 Mylpf 11668.4 41910.5 43208.6 CEM 1 + Myl1 4004.2 19948.0 25390.9 Top 10 Genes Ckm 17995.1 43811.5 46986.4 Acta1 30453.4 52098.6 52245.9 Mybpc2 2431.0 9248.7 13326.0 Ldb3 1424.6 9313.0 10952.4

Null module Ankrd1 Kat2b GEO Series "GSE49122" 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=GSE49122 Status: Public on Jul 23 2013 Title: Otitis Media Impact on Inner Ear Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24124478 Summary & Design: Summary: Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.

Methods: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.

Results: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.

Conclusion: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.

Overall design: There are 6 control samples and 8 samples trans-tympanically injected with H flu 10e9 for 6 hours. Each sample is a pool of 4 animals

Background corr dist: KL-Divergence = 0.0179, L1-Distance = 0.0166, L2-Distance = 0.0003, Normal std = 0.7467

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

IE controlIE TTrep Hflu 1IE (0.105227) control6 hrsIE rep controlrep 1 2(0.0792101)IE (0.0446386) TTrep Hflu 3IE (0.066174) TT6 hrs HfluIE rep control6 hrs2 (0.0373036)IE rep TTrep 3 Hflu 4(0.0387287)IE (0.0255395) control6 hrsIE rep TTrep 4 Hflu 5(0.00744877)IE (0.0417091) TT6 hrs HfluIE rep TT6 hrs5 Hflu (0.107013)IE rep TT6 hrs6 Hflu (0.0102423)IE rep control6 hrs7 (0.156615) rep rep 8 6(0.24583) (0.0343207) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 1266.6 4395.0 6493.0 P ( S | Z, I ) = 1.00 Ryr1 735.5 1917.9 2960.9 Mean Corr = 0.81751 Casq1 278.4 905.8 1438.8 Tcap 678.2 2110.3 3800.1 Mypn 34.7 123.2 223.2 Cacna1s 32.9 92.3 159.9 Ttn 41.4 124.4 200.2 Ankrd23 119.1 299.5 561.6 Smtnl1 41.3 97.4 172.3 Aldoa 8591.7 9044.4 9973.2 Actc1 34.1 193.2 650.8 Myl3 45.8 89.2 300.8 Ankrd2 140.4 311.6 554.7 Tnnt3 1339.6 5205.6 7367.1 Tnni2 1487.3 5823.6 8321.4 Tnnc2 2015.6 6445.3 9232.5 Myot 224.7 673.7 1428.7 Mylpf 1791.7 6017.8 8498.5 CEM 1 + Myl1 1102.7 3973.2 6910.3 Top 10 Genes Ckm 129.8 542.8 1093.5 Acta1 1222.0 4035.6 6441.3 Mybpc2 199.4 590.8 1079.3 Ldb3 168.0 697.8 1413.5

Null module Ankrd1 Kat2b GEO Series "GSE11990" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11990 Status: Public on Jul 20 2010 Title: Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy (training dataset) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20630075 Summary & Design: Summary: The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.

Overall design: Control skin was compared with skin tumors arising in k14Cre;p53loxP/loxP and k14Cre;p53loxP/loxP;pRbloxP/loxP animals, giving a mouse p53-tumor signature

Background corr dist: KL-Divergence = 0.1609, L1-Distance = 0.0435, L2-Distance = 0.0043, Normal std = 0.3697

1.079 Kernel fit Pairwise Correlations Normal fit

Density 0.540

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_skin_1control_skin_2 control_skin_3(0.0709184) control_skin_4(0.139488) control_skin_5(0.0934447) p53_tumor_1(0.0820181) p53_tumor_2(0.278114) (0.0161876)p53_tumor_3 (0.040803)p53_tumor_4 (0.0194452)p53_tumor_5 (0.0108565)p53_tumor_6 (0.0243465)p53_tumor_7 (0.0124369)p53_pRb_tumor_1 (0.0346719)p53_pRb_tumor_2p53_pRb_tumor_3 (0.0206041)p53_pRb_tumor_4 (0.0155973)p53_pRb_tumor_5 (0.0537835)p53_pRb_tumor_6 (0.0184584)p53_pRb_tumor_7 (0.0163758)p53_pRb_tumor_8 (0.0222033) (0.0154364) (0.0148095)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 60.9 247.3 39194.6 P ( S | Z, I ) = 1.00 Ryr1 35.6 96.0 10772.4 Mean Corr = 0.81591 Casq1 39.0 68.5 19882.2 Tcap 96.0 156.6 9561.6 Mypn 36.0 66.5 4797.4 Cacna1s 38.4 73.0 3443.1 Ttn 30.1 41.6 1212.4 Ankrd23 90.6 219.8 6113.0 Smtnl1 44.4 73.3 1532.8 Aldoa 3781.1 12732.9 35575.9 Actc1 57.4 93.3 3225.3 Myl3 130.7 161.2 292.5 Ankrd2 93.4 176.1 1397.9 Tnnt3 45.8 86.4 38376.0 Tnni2 92.2 413.2 42205.8 Tnnc2 38.1 341.2 50069.7 Myot 21.2 44.0 8761.7 Mylpf 76.9 266.3 37301.5 CEM 1 + Myl1 47.4 169.8 38893.1 Top 10 Genes Ckm 76.3 270.7 46135.8 Acta1 128.8 577.3 57461.9 Mybpc2 23.1 62.2 18137.2 Ldb3 45.5 85.2 10369.6

Null module Ankrd1 Kat2b GEO Series "GSE32316" 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=GSE32316 Status: Public on Jan 06 2012 Title: FGFR1 target genes in brown adipose tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22174314 Summary & Design: Summary: We aimed to identify genes that are regulated by FGFR1 in brown adipose tissues of adult male ob/ob mice by injecting 1 mg/kg anti-FGFR1 agonistic antibody.

Overall design: Brown adipose tissues were isolated from adult male ob/ob mice at day 4 after a single intraperitoneal injection of 1 mg/kg anti-FGFR1 agonistic antibody or pair-fed mice injected with control IgG. N=6 mice per each group.

Background corr dist: KL-Divergence = 0.1245, L1-Distance = 0.0368, L2-Distance = 0.0026, Normal std = 0.3996

0.998 Kernel fit Pairwise Correlations Normal fit

Density 0.499

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 controlIgG_rep1 controlIgG_rep2 (0.0777267) controlIgG_rep3 (0.110836) controlIgG_rep4 (0.010419) controlIgG_rep5 (0.0355668) anti-FGFR1_rep1IgG_rep6 (0.164003)anti-FGFR1_rep2 (0.127937)anti-FGFR1_rep3 (0.0292935)anti-FGFR1_rep4 (0.108211)anti-FGFR1_rep5 (0.036261)anti-FGFR1_rep6 (0.0166361) (0.203092) (0.0800182) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 338.2 5671.2 8837.0 P ( S | Z, I ) = 1.00 Ryr1 115.5 1081.6 2185.8 Mean Corr = 0.80616 Casq1 316.7 695.9 1074.3 Tcap 321.8 3207.1 4854.3 Mypn 79.1 346.9 550.7 Cacna1s 65.3 183.5 364.9 Ttn 41.3 66.2 102.2 Ankrd23 731.1 1617.9 2481.4 Smtnl1 67.1 162.5 275.1 Aldoa 24446.4 25475.9 27864.5 Actc1 265.2 333.4 446.5 Myl3 180.0 552.1 1061.5 Ankrd2 212.6 590.2 1329.4 Tnnt3 53.8 1711.8 3058.9 Tnni2 124.0 3521.1 6085.5 Tnnc2 98.7 4177.0 8392.3 Myot 36.8 1207.5 3348.1 Mylpf 99.0 1452.9 3907.6 CEM 1 + Myl1 3457.7 5469.8 8232.2 Top 10 Genes Ckm 188.5 2791.0 5679.6 Acta1 363.2 15071.4 19769.3 Mybpc2 91.6 589.4 1247.0 Ldb3 108.7 686.2 1794.6

Null module Ankrd1 Kat2b GEO Series "GSE24207" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 73 -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=GSE24207 Status: Public on Nov 18 2010 Title: mRNA analysis in different mouse tissues Organism: Mus musculus Experiment type: Third-party reanalysis Platform: GPL1261 Pubmed ID: 21088282 Summary & Design: Summary: The functioning of a specific tissue depends on the expression pattern of the different genes. We used microarrays to compare gene expression across different murine tissues, to get a better understanding in the expression pattern and functioning of the different tissues. With this analysis, we were not only able to identify genes that were specifically expressed in a spicific tissue but, as important, we also identified genes that were specifically repressed in a tissue, compared to al the other analysed tissues.

Overall design: For every tissue, at least 3 biological replicates were used.

Background corr dist: KL-Divergence = 0.3994, L1-Distance = 0.0931, L2-Distance = 0.0289, Normal std = 0.2840

1.542 Kernel fit Pairwise Correlations Normal fit

Density 0.771

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 diaphragm,Mouse diaphragm,Mouse biological diaphragm,Mouse biological spleen,replicateMouse biological spleen,replicateMousebiological 1 (0.128416) spleen,replicateMousebiological 2 replicate(0.121592) muscle,Mousebiological 3 replicate(0.134363) 1 (0.00177441)muscle,Mouse biological replicate 2 (0.0015686)muscle,Mouse biological replicate 3 (0.00160746)muscle,Mouse biological replicate 1 liver,(0.0651883)Mouse biological replicate biological2 liver,(0.0825356)Mouse replicate biological3 liver,(0.0702196)Mouse replicate biological4 brain,(0.073719)Mouse replicate 1 (0.00350979) biological brain,Mouse replicate 2 (0.00289724) biological brain,Mouse replicate 3 (0.00218923) biological lung,Mouse replicate 1 (0.00234485)biological lung,Mouse replicate 2 (0.00262109)biological lung,Mouse replicate 3 (0.00274937)biological kidney,Mouse replicate 1 (0.00319298) kidney,Mousebiological replicate 2 (0.00301894) kidney,Mousebiological 3replicate (0.00181079) adrenalMousebiological replicate 1 (0.00233509)adrenal Mousegland, replicate 2 (0.00142983)biologicaladrenal Mousegland, 3 (0.0042093)biologicalbone Mousegland, replicate marrow, biologicalboneMouse replicate 1 marrow, (0.00161679) biologicalboneMouse replicate 2 marrow, (0.00183588) biologicalboneMouse replicate 3 marrow, (0.00143323) biologicaladiposeMouse replicate 1 (0.00218143) biologicaladiposeMouse tissue, replicate 2 (0.00251907) adiposeMouse biologicaltissue, replicate 3 (0.00221201) pituitaryMouse biologicaltissue, replicate4 (0.00203774) pituitaryMouse biologicalgland, replicate 1 (0.00134231)pituitaryMouse biological gland, replicate 2 (0.0033758)pituitaryMouse biological gland, replicate 3 (0.00174078)pituitaryMouse biological gland, replicate 1 (0.00217903)salivaryMouse biological gland, replicate 2 (0.00255484)salivaryMouse biologicalgland, replicate 3 (0.00232174)salivaryMousebiological gland, replicate 4 (0.00309204)seminalMousebiological gland, replicate 5 (0.00190427)seminalMousebiological vesicle, replicate 1 (0.00120319) seminalMouse vesicle, biological replicate 2 (0.0019316) thymus,Mouse vesicle, biological replicate3 (0.00267579) thymus,Mouse biologicalbiological replicate 1 thymus,Mouse (0.00454454)biological replicatereplicate 2 testis,Mouse (0.00715162)biological replicate 13biological testis,Mouse (0.00266808)(0.0062878) replicate 2 biological testis,Mouse(0.00324667) replicate 3 biological heart,Mouse(0.00255851) replicate 1 (0.00178557)biological heart,Mouse replicate 2 (0.00176826)biological heart,Mouse replicate 3 (0.0015075)biological smallMouse replicate 1 (0.037481)intestine, smallMouse replicate 2 (0.0821243)intestine, smallMouse biological 3 (0.0567607)intestine, eye,Mouse biological replicate biological eye,Mouse biological replicate biological 1 (0.00199908)eye,Mousereplicate replicate biological 2 (0.00169319)placenta,Mousereplicate 1 (0.00100817) 3 (0.00210963)placenta,Mousereplicate 2biological (0.00110564) placenta,Mouse 3biological (0.00148161) replicate ovary,Mouse biological replicate biological 1ovary,Mouse (0.00248437) replicate biological 2ovary,Mouse (0.00337216) replicate biological 3pancreaticMouse (0.00252331) replicate 1 (0.00193979) pancreaticMouse replicate acini,2 (0.00221821) pancreaticMouse biological acini,3 (0.00174875) pancreaticMouse biological acini, replicate pancreaticMouse biological islets, replicate 1pancreaticCell-line, (0.0013994) biological islets, replicate 2Cell-line, (0.00250387) MIN6, biological islets, replicate 3Cell-line, biological(0.00298071) MIN6, biological replicate 1 biological (0.00167364)MIN6, replicate replicate 2 biological (0.00175316) replicate 1 (0.00149778)3 (0.00166294) replicate 2 (0.00154746)[ min 3 (0.00196242) ] [ medium ] [ max ] CEM 1 Atp2a1 6.7 120.5 75250.7 P ( S | Z, I ) = 1.00 Ryr1 3.3 80.2 41328.9 Mean Corr = 0.79792 Casq1 26.8 123.8 40563.4 Tcap 70.2 187.4 39483.9 Mypn 3.3 33.5 13988.0 Cacna1s 3.3 43.5 7042.6 Ttn 3.3 16.7 4206.3 Ankrd23 10.0 100.3 26491.7 Smtnl1 3.3 30.1 3625.7 Aldoa 3001.9 9063.0 78580.6 Actc1 10.0 117.1 70137.2 Myl3 23.5 170.6 60545.6 Ankrd2 6.7 80.4 7828.2 Tnnt3 3.3 46.8 93523.8 Tnni2 3.3 33.4 86897.6 Tnnc2 3.3 26.8 65618.1 Myot 3.3 33.4 47853.1 Mylpf 13.4 133.7 76876.2 CEM 1 + Myl1 3.3 70.2 78731.4 Top 10 Genes Ckm 6.7 90.4 82008.1 Acta1 3.3 261.0 80177.6 Mybpc2 3.3 46.8 52721.1 Ldb3 3.3 67.0 34469.0

Null module Ankrd1 Kat2b 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 (0.306453)Skin_Normal_4 (0.168325)Rb_p107_carcinoma_rep1 (0.089816)Rb_p107_carcinoma_rep2 (0.095403)Rb_p107_carcinoma_rep3Rb_p107_carcinoma_rep4 (0.0362522)Rb_p107_carcinoma_rep5 (0.0178835)Rb_p107_carcinoma_rep6 (0.0537017)Rb_p107_carcinoma_rep7 (0.0327686)Rb_p107_carcinoma_rep8 (0.0267492)Rb_p107_carcinoma_rep9 (0.0283485)Rb_p107_carcinoma_rep10 (0.0257785) (0.0359131) (0.0350656) (0.047542)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 412.1 2407.4 46534.3 P ( S | Z, I ) = 1.00 Ryr1 187.6 743.9 9654.3 Mean Corr = 0.79069 Casq1 143.0 580.8 13649.5 Tcap 385.1 2246.0 16756.3 Mypn 102.4 377.3 4315.1 Cacna1s 86.6 265.6 2808.8 Ttn 63.4 186.7 1346.1 Ankrd23 125.4 375.4 3847.8 Smtnl1 80.8 230.1 1905.7 Aldoa 15581.2 17806.7 41899.5 Actc1 74.8 147.8 485.8 Myl3 76.5 97.0 131.3 Ankrd2 206.1 288.5 434.0 Tnnt3 1000.9 5326.7 38193.1 Tnni2 1721.2 7129.1 41688.2 Tnnc2 2884.1 12281.6 57163.5 Myot 139.8 1104.8 11696.7 Mylpf 2111.1 7847.9 35829.8 CEM 1 + Myl1 2533.4 11266.0 45528.4 Top 10 Genes Ckm 770.8 4812.7 42404.4 Acta1 3110.4 9941.9 45843.6 Mybpc2 245.5 429.2 17452.1 Ldb3 136.0 600.7 10825.9

Null module Ankrd1 Kat2b 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 (0.0352974)TICNX_48h_rep4 (0.00947609)TICNX_96h_rep1 (0.179578)TICNX_96h_rep2 (0.0227575)TICNX_96h_rep3 (0.0421433)MTB/TICNX_48h_rep1 (0.0390517)MTB/TICNX_48h_rep2 (0.298833)MTB/TICNX_48h_rep3 MTB/TICNX_48h_rep4(0.0262905) MTB/TICNX_96h_rep1(0.0446093) MTB/TICNX_96h_rep2(0.0326361) MTB/TICNX_96h_rep3(0.0656684) MTB/TICNX_96h_rep4(0.0259533) (0.0828117) (0.0420321) (0.0528613)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 59.0 870.0 10280.8 P ( S | Z, I ) = 1.00 Ryr1 42.0 249.6 3362.6 Mean Corr = 0.78851 Casq1 32.8 442.1 6309.8 Tcap 81.3 642.4 6761.3 Mypn 47.0 142.0 1853.8 Cacna1s 30.6 73.9 933.4 Ttn 41.3 61.2 633.1 Ankrd23 140.6 265.0 1824.9 Smtnl1 31.9 69.0 578.8 Aldoa 11473.0 18966.9 28623.9 Actc1 39.1 51.0 152.6 Myl3 91.5 113.1 122.6 Ankrd2 81.9 106.7 146.3 Tnnt3 36.5 1967.2 21708.1 Tnni2 45.5 2125.0 22437.9 Tnnc2 71.9 5296.4 34800.3 Myot 21.8 460.9 6827.9 Mylpf 75.2 2309.9 25218.9 CEM 1 + Myl1 488.0 4244.5 33168.7 Top 10 Genes Ckm 54.0 2334.7 25445.0 Acta1 94.5 6379.7 35536.7 Mybpc2 29.8 805.7 9586.3 Ldb3 51.2 205.2 2980.9

Null module Ankrd1 Kat2b GEO Series "GSE4786" 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=GSE4786 Status: Public on May 01 2007 Title: Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16890326 Summary & Design: Summary: Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Caloric restricted mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed significantly fewer TUNEL-positive staining cells and fewer cleaved caspase-3-positive staining cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 28 proapoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR or staying lean can retard this process by suppressing apoptosis in the inner ear tissue.

Keywords: Effect of aging, effect of caloric restriction, time course, disease state analysis

Overall design: Quality control measures were not used. No replicates were done. Dye swap was not used.

Background corr dist: KL-Divergence = 0.0422, L1-Distance = 0.0248, L2-Distance = 0.0009, Normal std = 0.5870

0.680 Kernel fit Pairwise Correlations Normal fit

Density 0.340

0.000 CEM 1

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

Pre-normalization Quantiles

Cochlea_CR_15mo_1Cochlea_CR_15mo_2Cochlea_CR_15mo_3 (0.104343)Cochlea_MC_15mo_1 (0.125737)Cochlea_MC_15mo_2 (0.137418)Cochlea_MC_15mo_3 (0.140419)Cochlea_YC_4mo_1 (0.0418466)Cochlea_YC_4mo_2 (0.201558)Cochlea_YC_4mo_3 (0.0377351) (0.0498197) (0.161124)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 11495.7 33822.6 64602.4 P ( S | Z, I ) = 1.00 Ryr1 1500.8 5270.2 11352.1 Mean Corr = 0.78259 Casq1 1292.5 5309.0 11158.0 Tcap 1803.1 5806.0 14364.9 Mypn 464.6 1289.8 2372.7 Cacna1s 339.0 629.9 1688.6 Ttn 158.8 704.0 1373.6 Ankrd23 370.0 1459.6 2970.0 Smtnl1 146.4 529.6 861.6 Aldoa 24118.8 47210.4 69583.9 Actc1 409.9 1367.6 3937.7 Myl3 84.3 293.4 1136.5 Ankrd2 159.4 678.3 1657.4 Tnnt3 3879.5 14548.6 35027.5 Tnni2 5728.1 18502.3 38703.0 Tnnc2 14215.0 43372.7 83728.5 Myot 1833.7 4409.9 6915.9 Mylpf 8214.3 22041.3 40143.8 CEM 1 + Myl1 7380.8 14806.1 38990.8 Top 10 Genes Ckm 8625.3 28577.6 54375.4 Acta1 11988.3 31047.0 65317.0 Mybpc2 2123.2 5098.8 15073.4 Ldb3 776.5 2669.4 5693.0

Null module Ankrd1 Kat2b GEO Series "GSE13563" 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=GSE13563 Status: Public on Nov 15 2008 Title: Pilot study: Basal gene expression in bone Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23182809 Summary & Design: Summary: Pilot study

Analysis of basal gene expression of the protective bones of the skull (parietals), weight-bearing bones of the limb (ulnae) and mandibular bone and teeth #!#

Overall design: RNA extraction from normal bone

Background corr dist: KL-Divergence = 0.0312, L1-Distance = 0.0280, L2-Distance = 0.0008, Normal std = 0.6863

0.603 Kernel fit Pairwise Correlations Normal fit

Density 0.301

0.000 CEM 1

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

Pre-normalization Quantiles

CalvarialCalvarial bone_1Mandible_1 bone_2(0.246081)Mandible_2 (0.257237) (0.061946)Ulna_1 (0.0359886) Ulna_2(0.216724) (0.182023) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 2245.7 17053.9 20305.0 P ( S | Z, I ) = 1.00 Ryr1 303.6 3724.8 4977.5 Mean Corr = 0.77789 Casq1 621.7 4948.0 6455.0 Tcap 655.3 5960.2 11129.7 Mypn 120.2 1259.0 1291.4 Cacna1s 28.5 566.7 805.0 Ttn 40.8 444.7 710.3 Ankrd23 110.6 1469.8 2319.4 Smtnl1 97.4 870.9 1146.3 Aldoa 7995.0 24923.2 31964.9 Actc1 174.2 308.5 1126.1 Myl3 18.8 119.4 177.2 Ankrd2 125.4 344.0 1125.9 Tnnt3 3012.2 24186.6 31827.5 Tnni2 3409.4 28988.7 31689.9 Tnnc2 9217.1 41246.7 45122.2 Myot 637.1 8809.6 11813.6 Mylpf 4603.4 29121.3 33106.6 CEM 1 + Myl1 6366.4 40621.3 42289.9 Top 10 Genes Ckm 3330.5 22130.4 27894.6 Acta1 6122.8 42686.5 44166.5 Mybpc2 536.8 4437.3 6337.1 Ldb3 394.5 3308.5 4421.2

Null module Ankrd1 Kat2b GEO Series "GSE25295" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 25 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE25295 Status: Public on Nov 17 2010 Title: Critical Role of Sphingolipid Pathway Components in Murine Radiation-Induced Lung Injury: Protection by Sphingosine-1-Phosphate Analogues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21712494 Summary & Design: Summary: Clinically significant radiation-induced lung injury (RILI) is associated with significant morbidity and mortality and a common toxicity in patients administered thoracic radiotherapy. While the molecular etiology of RILI is poorly understood, we previously characterized a murine model of RILI in which alterations in lung endothelial barrier integrity surfaced as a potentially important pathobiologic event. In these studies, inhibition of HMG-CoA reductase activity (simvastatin) reduced murine RILI-associated lung inflammation and vascular leak and attenuated radiation-induced dysregulation of sphingolipid metabolic pathway genes identified by genome-wide lung gene expression profiling. In the present study, we test the hypothesis that sphingolipid signaling components serve as important modulators of RILI pathobiology and novel therapeutic targets. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to cumulative sphingosine-1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue following 25 Gy exposure (6 weeks). Moreover, genetically-engineered mice with either targeted deletion of SphK1 (SphK1-/-), or with reduced expression of selective members of the S1P receptor family (S1PR1+/-, S1PR2-/-, S1PR3-/-,), exhibited marked susceptibility to RILI-mediated lung inflammation. Finally, we assessed the efficacy of three potent vascular barrier-protective S1P analogues FTY720 (FTY), fTysiponate (fTyS) and SEW-2871 (SEW) in attenuating indices of RILI. The phosphonate analogue, fTyS, and to a lesser degree SEW, exhibited significant attenuation of RILI and RILI-induced gene dysregulation compared to control RILI-challenged mice (6 weeks). In contrast, FTY failed to significantly alter physiologic or genomic changes compared to RILI-challenged controls. Together, these results support the targeting of sphingolipid components as a novel and effective therapeutic strategy in RILI.

Overall design: Four mice were treated with PBS as a control. Three mice were treated with (S)-FTY-phosphonate (0.1mg/kg) as a drug control. Three mice were treated with SEW-2871 (0.1mg/kg) as a drug control. Three mice were treated with FTY720 (0.1mg/kg) as a drug control. Three mice were treated with administered radiation (25 Gy) alone. Three mice were treated with both administered radiation (25 Gy) and (S)-FTY-phosphonate (0.1mg/kg). Three mice were treated with both administered radiation (25 Gy) and SEW-2871 (0.1mg/kg). Three mice were treated with both administered radiation (25 Gy) and FTY720 (0.1mg/kg).

Background corr dist: KL-Divergence = 0.2603, L1-Distance = 0.0508, L2-Distance = 0.0060, Normal std = 0.2985

1.336 Kernel fit Pairwise Correlations Normal fit

Density 0.668

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,Control, rep1 (0.0322587)Control, rep2 (0.0202145)Control, rep3 (0.0208063)Drug rep4 control (0.0210311)Drug controlfTyS,Drug rep1 controlfTyS,Drug (0.0224256) rep2 controlfTyS,Drug (0.299259) rep3 controlSEW,Drug (0.0122343) rep1 controlSEW,Drug (0.0266456) rep2 controlSEW,Drug (0.0165394) rep3 controlFTY,Drug (0.0263765) rep1 controlFTY,Radiation (0.0154353) rep2 FTY,Radiation (0.0128331) alone, rep3Radiation (0.0125011) rep1 alone, (0.0253987)Radiation rep2 alone, (0.0109398)Radiation rep3 with (0.0140104)RadiationfTyS, with rep1 RadiationfTyS, with (0.0290994) rep2 RadiationfTyS, with (0.0328576) rep3 RadiationSEW, with (0.0130345) rep1 RadiationSEW, with (0.0215407) rep2 RadiationSEW, with (0.0344981) rep3 RadiationFTY, with (0.0161122) rep1 FTY, with(0.114092) rep2 FTY, (0.021358) rep3 (0.128498)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 38.0 103.9 5042.9 P ( S | Z, I ) = 1.00 Ryr1 33.7 70.2 2295.2 Mean Corr = 0.77139 Casq1 48.2 82.0 2191.5 Tcap 357.3 1114.9 4849.1 Mypn 69.8 143.5 1067.4 Cacna1s 22.1 50.4 554.5 Ttn 25.1 58.9 501.7 Ankrd23 62.8 100.0 2750.7 Smtnl1 32.2 50.3 1099.1 Aldoa 4641.8 5743.5 9618.0 Actc1 4444.1 7695.9 9858.7 Myl3 97.8 237.1 5692.6 Ankrd2 9.7 24.6 726.6 Tnnt3 19.1 135.1 9686.2 Tnni2 28.1 104.0 10488.2 Tnnc2 19.8 164.8 7877.2 Myot 5.9 30.9 4879.3 Mylpf 47.5 125.4 9652.6 CEM 1 + Myl1 44.2 633.4 7814.3 Top 10 Genes Ckm 185.3 949.4 9995.9 Acta1 144.6 345.9 13084.8 Mybpc2 35.8 69.7 3196.2 Ldb3 140.7 402.0 2893.9

Null module Ankrd1 Kat2b GEO Series "GSE32422" 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=GSE32422 Status: Public on Jan 06 2013 Title: Expression data from the dorsal and lateral lobes of the prostates of TRAMP mice treated with OSU-CG5 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23275006 Summary & Design: Summary: Cells undergoing malignant transformation often shift their cellular metabolism from primarily oxidative phosphorylation to aerobic glycolysis (the Warburg effect). Energy restriction-mimetic agents (ERMAs), such as 2-deoxyglucose and resveratrol, that target this shift in cellular metabolism have been effective in inhibiting cancer cell growth in vitro, and xenograft tumor growth in vivo.

We recently developed a novel ERMA, OSU-CG5, that exhibits higher in vivo activity than previously described ERMAs. In this study, we investigated the effect of OSU-CG5 on global gene expression in the dorsal and lateral lobes of the prostate of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, and on its ability to suppress lesion progression in these mice.

Overall design: Intact male TRAMP mice were randomized into 2 groups and treated for 4-weeks (from age 6 to 10 weeks) with a vehicle or 100 mg/kg/day OSU-CG5 via oral gavage. At the end of the study, the urogenital tracts were collected and prostates microdissected. RNA was extracted from the dorsal and lateral lobes of the prostates from 3 mice per group, and Affymetrix microarrays were performed.

Background corr dist: KL-Divergence = 0.0283, L1-Distance = 0.0131, L2-Distance = 0.0002, Normal std = 0.6752

0.591 Kernel fit Pairwise Correlations Normal fit

Density 0.295

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

CG5-100-121.Lisa.rma-SignalCG5-100-123.Lisa.rma-SignalCG5-100-141.Lisa.rma-SignalVehicle-115.Lisa.rma-Signal (0.249008)Vehicle-117.Lisa.rma-Signal (0.0670494)Vehicle-99.Lisa.rma-Signal (0.0976782) (0.154873) (0.387241) (0.0441498)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 136.1 189.4 239.7 P ( S | Z, I ) = 1.00 Ryr1 42.6 60.8 87.8 Mean Corr = 0.76566 Casq1 62.2 97.0 126.0 Tcap 167.1 185.7 225.8 Mypn 58.4 74.0 81.1 Cacna1s 38.5 51.2 55.6 Ttn 28.9 40.3 54.7 Ankrd23 245.1 318.1 366.2 Smtnl1 44.3 50.7 57.5 Aldoa 740.8 854.0 1393.1 Actc1 81.6 98.5 132.7 Myl3 244.7 280.3 328.5 Ankrd2 166.5 207.4 220.8 Tnnt3 42.9 57.4 93.7 Tnni2 83.3 137.3 156.9 Tnnc2 1327.0 2699.5 3098.3 Myot 30.9 38.5 47.0 Mylpf 135.3 340.9 376.1 CEM 1 + Myl1 75.0 177.2 220.8 Top 10 Genes Ckm 158.2 249.2 313.2 Acta1 921.1 1511.9 2195.6 Mybpc2 50.5 71.3 112.7 Ldb3 44.5 60.8 84.9

Null module Ankrd1 Kat2b GEO Series "GSE19616" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19616 Status: Public on Jul 20 2010 Title: Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy (testing dataset) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20630075 Summary & Design: Summary: The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.

Overall design: Control skin was compared with skin tumors arising in k14Cre;p53loxP/loxP and k14Cre;p53loxP/loxP;pRbloxP/loxP animals, giving a mouse p53-tumor signature

Background corr dist: KL-Divergence = 0.1802, L1-Distance = 0.0477, L2-Distance = 0.0056, Normal std = 0.3576

1.116 Kernel fit Pairwise Correlations Normal fit

Density 0.558

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_skin_1Control_skin_2Control_skin_3 (0.249659)Control_skin_4 (0.162688)p53_tumor1 (0.118008)p53_tumor2 (0.0864674) (0.0210901)p53_tumor3 (0.0217125)p53_tumor4 (0.0283208)p53_tumor5 (0.0272704)p53_tumor6 (0.0245)p53_tumor7 (0.0233977)pRbp53_tumor1 (0.0368034)pRbp53_tumor2pRbp53_tumor3 (0.0307209)pRbp53_tumor4 (0.0431889)pRbp53_tumor5 (0.0187091) (0.0550183) (0.052445) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 81.8 120.8 36601.5 P ( S | Z, I ) = 1.00 Ryr1 36.2 127.8 8264.6 Mean Corr = 0.76183 Casq1 87.2 170.4 13287.4 Tcap 81.6 130.0 10176.8 Mypn 28.7 40.2 3109.9 Cacna1s 35.7 60.5 2067.0 Ttn 29.9 37.0 974.2 Ankrd23 164.5 291.7 5909.1 Smtnl1 26.4 40.3 1066.6 Aldoa 4923.1 14163.9 35236.4 Actc1 40.2 67.8 420.7 Myl3 99.1 124.5 169.2 Ankrd2 118.4 173.6 376.3 Tnnt3 42.3 144.9 21533.1 Tnni2 80.6 319.3 41099.4 Tnnc2 52.6 295.6 42946.6 Myot 23.4 31.4 10198.5 Mylpf 51.8 173.3 23714.6 CEM 1 + Myl1 43.8 187.6 32135.1 Top 10 Genes Ckm 95.8 139.8 33892.0 Acta1 89.8 890.0 50845.6 Mybpc2 49.5 91.7 18966.9 Ldb3 35.0 46.0 6959.5

Null module Ankrd1 Kat2b GEO Series "GSE4866" 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=GSE4866 Status: Public on May 18 2007 Title: The role of mtDNA mutations in age-related hearing loss in mice carrying a mutator DNA polymerase gamma Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17363114 Summary & Design: Summary: Mitochondrial DNA (mtDNA) mutations may contribute to aging and age-related disorders. Previously, we created mice expressing a proofreading-deficient version of the mtDNA polymerase gamma (Polg) which accumulate age-related mtDNA mutations and display premature aging. Here we performed microarray gene expression profiling to identify mtDNA mutation-responsive genes in the cochlea of aged mitochondrial mutator mice. Age-related accumulation of mtDNA mutations was associated with transcriptional alternations consistent with reduced inner ear function, mitochondrial dysfunction, neurodegeneration, and reduced cell structural modulation. Hearing assessment and histopathological results confirmed that aged PolgD257A/D257A (D257A) mice exhibited moderate hearing loss and severe cochlear degenerations. Age-related accumulation of mtDNA mutations also resulted in alternations in gene expression consistent with induction of apoptosis, proteolysis, stress response, and reduced DNA repair. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay confirmed that the cochleae from aged D257A mice showed significantly more TUNEL positive cells compared to wild-type (WT) mice. The levels of cleaved caspase-3 were also found to increase in the cochleae of aged D257A mice. These observations provide evidence that age-related accumulation of mtDNA mutations is associated with apoptotic cell death in aged cochlea. Our results provide the first global view of molecular events associated with mtDNA mutations in postmitotic tissue, and suggest that apoptosis is the major mechanism of mtDNA mediated cell death in the development of age-related hearing disorder.

Keywords: disease state analysis

Overall design: Affymetrix standard spike controls were used in all experiments (eukaryotic hybridization control kit). Quality control measures were not used. No replicates were done. Dye swap was not used.

Background corr dist: KL-Divergence = 0.0920, L1-Distance = 0.0291, L2-Distance = 0.0015, Normal std = 0.4506

0.885 Kernel fit Pairwise Correlations Normal fit

Density 0.443

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

Cochlea_WT_9mo_1Cochlea_WT_9mo_3Cochlea_WT_9mo_4 (0.304599)Cochlea_WT_9mo_5 (0.0561842)Cochlea_WT_9mo_2 (0.0535397)Cochlea_D257A_9mo_1 (0.123962)Cochlea_D257A_9mo_2 (0.0906147)Cochlea_D257A_9mo_3Cochlea_D257A_9mo_4 (0.106153)Cochlea_D257A_9mo_5 (0.0645472) (0.0849593) (0.069744) (0.0456974)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 433.9 10941.9 20556.9 P ( S | Z, I ) = 1.00 Ryr1 198.6 2127.9 3505.0 Mean Corr = 0.75993 Casq1 337.2 1141.4 4097.5 Tcap 481.3 2897.0 8914.9 Mypn 72.9 308.7 762.8 Cacna1s 60.4 322.6 722.9 Ttn 55.8 180.3 412.6 Ankrd23 52.1 696.6 2165.9 Smtnl1 11.9 230.5 682.8 Aldoa 11292.0 21861.9 32735.4 Actc1 111.4 896.8 2122.9 Myl3 43.7 127.0 189.0 Ankrd2 20.5 165.9 435.6 Tnnt3 175.9 3050.0 14364.1 Tnni2 120.1 3430.6 14011.0 Tnnc2 239.0 10521.1 22340.9 Myot 79.5 2184.1 4528.6 Mylpf 238.3 5491.1 14724.3 CEM 1 + Myl1 221.5 5472.5 14333.4 Top 10 Genes Ckm 338.3 13024.4 19469.9 Acta1 561.8 16520.8 21083.0 Mybpc2 71.9 2081.9 3147.4 Ldb3 163.5 828.6 2095.0

Null module Ankrd1 Kat2b GEO Series "GSE27309" 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=GSE27309 Status: Public on Mar 15 2011 Title: SIRT3 opposes metabolic reprogramming of cancer cells through HIF1a destabilization Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21397863 Summary & Design: Summary: Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.

Overall design: RNA isolated from brown adipose tissue of SIRT3 WT and KO mice. 5 wild-type samples and 5 SIRT3 KO samples

Background corr dist: KL-Divergence = 0.1165, L1-Distance = 0.0301, L2-Distance = 0.0015, Normal std = 0.4112

0.970 Kernel fit Pairwise Correlations Normal fit

Density 0.485

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

BAT_WT_1BAT_WT_2 (0.0868233)BAT_WT_3 (0.185094)BAT_WT_4 (0.12296)BAT_WT_5 (0.109914)BAT_KO_1 (0.108835)BAT_KO_2 (0.111675)BAT_KO_3 (0.063943)BAT_KO_4 (0.114897)BAT_KO_5 (0.0686599) (0.0271975) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 232.8 18521.8 20825.9 P ( S | Z, I ) = 1.00 Ryr1 30.3 1540.5 2121.7 Mean Corr = 0.74787 Casq1 84.7 2582.9 3215.2 Tcap 210.8 4105.1 6359.4 Mypn 44.7 372.8 482.2 Cacna1s 75.3 548.0 675.1 Ttn 111.9 258.6 340.1 Ankrd23 340.8 1603.2 3225.2 Smtnl1 58.0 416.0 565.9 Aldoa 32605.7 41356.1 42691.9 Actc1 215.3 304.8 512.1 Myl3 258.2 295.7 1558.4 Ankrd2 288.0 494.6 886.0 Tnnt3 84.4 11906.8 14865.1 Tnni2 103.2 10871.9 14505.5 Tnnc2 55.7 14556.5 19539.5 Myot 24.8 2645.9 4184.2 Mylpf 150.5 8642.5 12282.0 CEM 1 + Myl1 6478.8 19150.9 24513.7 Top 10 Genes Ckm 209.6 15039.4 19799.6 Acta1 219.7 35861.9 44843.7 Mybpc2 42.4 2180.1 3330.7 Ldb3 135.8 1308.0 2061.2

Null module Ankrd1 Kat2b GEO Series "GSE9954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 70 -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=GSE9954 Status: Public on Dec 20 2007 Title: Large-scale analysis of the mouse transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18365009 Summary & Design: Summary: We used microarrays to compare gene expression across different murine tissues.

Keywords: Other

Overall design: Different tissues were dissected from 10-12 week old C57Bl6 mice for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.3484, L1-Distance = 0.0923, L2-Distance = 0.0272, Normal std = 0.2989

1.449 Kernel fit Pairwise Correlations Normal fit

Density 0.724

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 diaphragm,Mouse diaphragm,Mouse biological diaphragm,Mouse biological spleen,replicateMouse biological spleen,replicateMousebiological 1 (0.106469) spleen,replicateMousebiological 2 replicate(0.113594) muscle,Mousebiological 3 replicate(0.110336) 1 (0.00234676)muscle,Mouse biological replicate 2 (0.00196644)muscle,Mouse biological replicate 3 (0.00217102)muscle,Mouse biological replicate 1 liver,(0.0854421)Mouse biological replicate biological2 liver,(0.0793503)Mouse replicate biological3 liver,(0.0804988)Mouse replicate biological4 brain,(0.0808528)Mouse replicate 1 (0.00302612) biological brain,Mouse replicate 2 (0.00442508) biological brain,Mouse replicate 3 (0.00256623) biological lung,Mouse replicate 1 (0.00295333)biological lung,Mouse replicate 2 (0.00300521)biological lung,Mouse replicate 3 (0.00280441)biological kidney,Mouse replicate 1 (0.00252345) kidney,Mousebiological replicate 2 (0.00131563) kidney,Mousebiological 3replicate (0.00168583) adrenalMousebiological replicate 1 (0.00308199)adrenal Mousegland, replicate 2 (0.00247032)biologicaladrenal Mousegland, 3 (0.00312236)biologicalbone Mousegland, replicate marrow, biologicalboneMouse replicate 1 marrow, (0.00174562) biologicalboneMouse replicate 2 marrow, (0.00212795) biologicalboneMouse replicate 3 marrow, (0.00167415) biologicaladiposeMouse replicate 1 (0.00206941) biologicaladiposeMouse tissue, replicate 2 (0.00197861) adiposeMouse biologicaltissue, replicate 3 (0.00223902) pituitaryMouse biologicaltissue, replicate4 (0.00222883) pituitaryMouse biologicalgland, replicate 1 (0.00162746)pituitaryMouse biological gland, replicate 2 (0.00417361)pituitaryMouse biological gland, replicate 3 (0.00200011)pituitaryMouse biological gland, replicate 1 (0.00296535)salivaryMouse biological gland, replicate 2 (0.00282449)salivaryMouse biologicalgland, replicate 3 (0.00263628)salivaryMousebiological gland, replicate 4 (0.0029901)seminalMousebiological gland, replicate 5 (0.00231166)seminalMousebiological vesicle, replicate 1 (0.00211223) seminalMouse vesicle, biological replicate 2 (0.00200944) thymus,Mouse vesicle, biological replicate3 (0.00192672) thymus,Mouse biologicalbiological replicate 1 thymus,Mouse (0.0067795)biological replicatereplicate 2 testis,Mouse (0.00685934)biological replicate 13biological testis,Mouse (0.00240239)(0.00416072) replicate 2 biological testis,Mouse(0.00280906) replicate 3 biological heart,Mouse(0.00293846) replicate 1 (0.00159023)biological heart,Mouse replicate 2 (0.00186716)biological heart,Mouse replicate 3 (0.00157211)biological smallMouse replicate 1 (0.0600548)intestine, smallMouse replicate 2 (0.0757954)intestine, smallMouse biological 3 (0.0515631)intestine, eye,Mouse biological replicate biological eye,Mouse biological replicate biological 1 (0.0020655)eye,Mousereplicate replicate biological 2 (0.00206347)ESMousereplicate 1 cells,(0.00154358) 3 (0.00236095)ESMousereplicate biological2 cells,(0.00147003) ESMouse biological3 cells,(0.00183152) replicate placenta,Mouse biological replicate 1 placenta,Mouse (0.00174158) biological replicate 2 placenta,Mouse (0.00192567) biological replicate 3 ovary,Mouse (0.00201199) biological replicate biological 1ovary,Mouse (0.00278408) replicate biological 2ovary,Mouse (0.0027918) replicate biological 3fetus,Mouse (0.00285975) replicate 1 (0.00222169)biological fetus,Mouse replicate 2 (0.00231259)biological fetus, replicate 3 (0.00219819)biological replicate 1 (0.00389193) replicate 2 (0.0038732)[ min3 (0.00401261) ] [ medium ] [ max ] CEM 1 Atp2a1 201.8 299.9 34660.5 P ( S | Z, I ) = 1.00 Ryr1 170.2 243.3 17803.5 Mean Corr = 0.74652 Casq1 187.9 280.8 18275.4 Tcap 214.8 344.7 24581.5 Mypn 163.2 225.8 7633.0 Cacna1s 165.5 230.0 3959.4 Ttn 137.8 197.9 3168.8 Ankrd23 238.4 327.4 14845.0 Smtnl1 161.0 242.6 2226.8 Aldoa 2095.1 7096.6 39051.0 Actc1 187.1 287.6 56736.0 Myl3 214.8 358.2 40572.9 Ankrd2 224.8 336.3 4735.6 Tnnt3 155.2 210.6 37632.1 Tnni2 192.1 251.0 42416.1 Tnnc2 175.5 233.1 40452.3 Myot 134.5 184.6 20362.6 Mylpf 200.9 307.6 40959.3 CEM 1 + Myl1 155.1 222.2 43265.0 Top 10 Genes Ckm 185.6 326.9 40330.8 Acta1 197.5 427.5 51859.7 Mybpc2 168.9 232.4 25044.0 Ldb3 169.7 266.1 15627.5

Null module Ankrd1 Kat2b GEO Series "GSE52358" 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=GSE52358 Status: Public on Jun 18 2014 Title: Gene expression profiling of the tongue bud from Alk5 mutant mouse models Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the tongue bud from mice at embryonic day E13.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.

Overall design: To investigate the adverse effects of dysfunctional TGF-beta signaling on tissue-tissue interactions between CNCCs and myogenic precursors of craniofacial muscles, we analyzed tongue bud tissue of mice with a CNCC-specific conditional inactivation of Alk5 (Wnt1-Cre; Alk5 fl/fl). We performed microarray analyses of the tongue bud of Alk5 fl/fl control mice and Wnt1-Cre; Alk5 fl/fl mutant mice, collected at embryonic day E13.5 (n=4 per group).

Background corr dist: KL-Divergence = 0.0605, L1-Distance = 0.0184, L2-Distance = 0.0004, Normal std = 0.5241

0.761 Kernel fit Pairwise Correlations Normal fit

Density 0.381

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 Alk5E13.5 fl/fl Alk5 controlE13.5 fl/fl Alk5 controlE13.5mouse fl/fl Alk5 controlE13.5tonguemouse fl/fl Wnt1-Cre;Alk5 controlE13.5tonguemousebud 1 Wnt1-Cre;Alk5(0.0392711) E13.5tonguemousebud 2 Wnt1-Cre;Alk5fl/fl(0.203377) E13.5tonguebud conditional 3 Wnt1-Cre;Alk5fl/fl(0.0687587) bud conditional 4 fl/fl (0.280689)knockout conditional fl/fl knockout mouseconditional knockout[ modelmousemin knockout tongue modelmouse ] tongue budmodelmouse 1 (0.0779988) tongue budmodel[ medium2 (0.0883173) tonguebud 3 (0.161232) bud 4 (0.0803556) ] [ max ] CEM 1 Atp2a1 395.3 496.4 613.3 P ( S | Z, I ) = 1.00 Ryr1 108.9 136.8 230.3 Mean Corr = 0.73379 Casq1 106.6 174.8 250.7 Tcap 131.0 210.3 268.2 Mypn 298.6 454.0 595.9 Cacna1s 104.6 162.7 200.7 Ttn 92.8 114.1 136.4 Ankrd23 45.9 52.1 61.6 Smtnl1 29.9 36.3 39.9 Aldoa 5134.8 6233.9 7334.8 Actc1 17207.1 23623.2 25042.4 Myl3 87.7 97.6 136.6 Ankrd2 95.5 141.4 218.8 Tnnt3 517.2 1449.6 1835.2 Tnni2 1036.9 2253.8 3017.3 Tnnc2 5071.6 11214.7 13859.0 Myot 401.5 900.3 1377.4 Mylpf 8726.9 16422.3 20328.3 CEM 1 + Myl1 9058.3 16026.9 19757.0 Top 10 Genes Ckm 78.2 100.7 166.6 Acta1 3027.3 6828.3 9563.7 Mybpc2 53.6 61.3 71.9 Ldb3 96.5 154.5 209.7

Null module Ankrd1 Kat2b GEO Series "GSE12248" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 83 -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=GSE12248 Status: Public on Dec 31 2008 Title: Genetic architecture of murine skin inflammation and tumor susceptibility Organism: Mus musculus x Mus spretus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19136944 Summary & Design: Summary: Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility.

Keywords: Expression Quantitative Trait Loci

Overall design: A backcross was generated using male Mus spretus and female FVB/N mice; female F1 hybrids were mated with male FVB/N mice. Seventy-one backcross mice (8-12 weeks old) received a single dose of DMBA (25 ´g per mouse in 200 ´l acetone). Starting one week after the initiation tumors were promoted with TPA (200 ´l of 10-4 M solution in acetone) twice weekly for 20 weeks. Initiation and promotion were performed on doral back skin. Normal tail skin was snap frozen when the animals were sacrificed. Tail epidermis from completely untreated Spretus, FVB, and Spretus x FVB F1 mice was also analyzed.

Background corr dist: KL-Divergence = 0.4400, L1-Distance = 0.0894, L2-Distance = 0.0259, Normal std = 0.2378

1.678 Kernel fit Pairwise Correlations Normal fit

Density 0.839

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

Tail-FVBBX-1Tail-FVBBX-2 (0.00244772)Tail-FVBBX-3 (0.0374859)Tail-FVBBX-4 (0.00517451)Tail-FVBBX-5 (0.00846427)Tail-FVBBX-6 (0.00244977)Tail-FVBBX-7 (0.00406947)Tail-FVBBX-8 (0.00967529)Tail-FVBBX-9 (0.00885903)Tail-FVBBX-10 (0.00391974)Tail-FVBBX-11 Tail-FVBBX-12(0.00643246) Tail-FVBBX-13(0.00639015) Tail-FVBBX-14(0.00491681) Tail-FVBBX-15(0.0134932) Tail-FVBBX-16(0.00311654) Tail-FVBBX-17(0.0294868) Tail-FVBBX-18(0.00324238) Tail-FVBBX-19(0.0060699) Tail-FVBBX-20(0.00318206) Tail-FVBBX-21(0.00706871) Tail-FVBBX-22(0.00396048) Tail-FVBBX-23(0.00752169) Tail-FVBBX-24(0.00250728) Tail-FVBBX-25(0.0558438) Tail-FVBBX-26(0.00246663) Tail-FVBBX-27(0.0043339) Tail-FVBBX-28(0.0132199) Tail-FVBBX-29(0.15223) Tail-FVBBX-30(0.00645179) Tail-FVBBX-31(0.00450585) Tail-FVBBX-32(0.00527959) Tail-FVBBX-33(0.00108011) Tail-FVBBX-34(0.00189631) Tail-FVBBX-35(0.00150956) Tail-FVBBX-36(0.00876741) Tail-FVBBX-37(0.00373682) Tail-FVBBX-38(0.00640915) Tail-FVBBX-39(0.00896287) Tail-FVBBX-40(0.000960297) Tail-FVBBX-41(0.0021399) Tail-FVBBX-42(0.00563399) Tail-FVBBX-43(0.00282279) Tail-FVBBX-44(0.00350206) Tail-FVBBX-45(0.00624152) Tail-FVBBX-46(0.00362149) Tail-FVBBX-47(0.00499003) Tail-FVBBX-49(0.00313051) Tail-FVBBX-50(0.00531617) Tail-FVBBX-51(0.00643259) Tail-FVBBX-52(0.00788485) Tail-FVBBX-53(0.0190591) Tail-FVBBX-54(0.00389344) Tail-FVBBX-55(0.00120031) Tail-FVBBX-56(0.00443651) Tail-FVBBX-58(0.0017221) Tail-FVBBX-59(0.0032566) Tail-FVBBX-60(0.00248005) Tail-FVBBX-61(0.00352484) Tail-FVBBX-62(0.00596126) Tail-FVBBX-63(0.00546162) Tail-FVBBX-64(0.00420734) Tail-FVBBX-65(0.0101065) Tail-FVBBX-66(0.00248027) Tail-FVBBX-67(0.0194318) Tail-FVBBX-68(0.0058238) Tail-FVBBX-69(0.0103061) Tail-FVBBX-70(0.00880785) Tail-FVBBX-71(0.00937776) Tail-FVBBX-72(0.0410656) Tail-FVBBX-73(0.00621106) Tail-FVB-1(0.00484261) Tail-FVB-2(0.00186596) (0.00599191)Tail-FVB-3 (0.00695545)Tail-FVB-4 (0.00666049)Tail-SpretusxFVB-1 (0.0102349)Tail-SpretusxFVB-2Tail-SpretusxFVB-3 (0.00886213)Tail-SpretusxFVB-4 (0.00757913)Tail-Spretus-1 (0.0779967)Tail-Spretus-2 (0.00593483) (0.0726949)Tail-Spretus-3 (0.0239811)Tail-Spretus-4 (0.0344842) (0.0537972) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 147.4 2260.3 14176.2 P ( S | Z, I ) = 1.00 Ryr1 48.7 190.6 1544.0 Mean Corr = 0.73171 Casq1 62.8 425.3 4088.3 Tcap 91.8 1101.0 7069.1 Mypn 71.0 249.4 2303.0 Cacna1s 42.1 77.3 464.3 Ttn 39.0 82.2 1400.4 Ankrd23 141.2 334.7 929.1 Smtnl1 60.8 170.9 1266.2 Aldoa 9928.8 15672.8 28685.2 Actc1 46.1 82.2 600.6 Myl3 122.1 266.2 1863.7 Ankrd2 137.8 322.8 2377.8 Tnnt3 67.1 1597.1 18418.4 Tnni2 122.6 2908.6 26286.3 Tnnc2 59.2 4449.0 36800.6 Myot 27.0 465.8 5380.7 Mylpf 126.4 3933.6 34631.6 CEM 1 + Myl1 55.2 4097.5 33417.5 Top 10 Genes Ckm 68.4 927.0 12368.9 Acta1 63.5 5182.0 33352.9 Mybpc2 38.2 65.4 425.2 Ldb3 64.1 244.2 1971.4

Null module Ankrd1 Kat2b GEO Series "GSE22307" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 23 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22307 Status: Public on Oct 13 2010 Title: Expression data from mouse colon tissue response to DSS induction at day 0, 2, 4 and 6 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20923862 Summary & Design: Summary: Temporal genome profiling of DSS colitis

The DSS induced mouse colitis model is often used to emulate Ulcerative Colitis (UC) in order understand pathophysiological mechanism of inflammatory bowel disease (IBD). Given the progressive nature of IBD, colon tissue gene expression changes during the evolution of disease, and knowing the changes in gene expression profiles could indentify potential diagnostic markers or additional therapeutic targets for colitis. Therefore, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis.

Keywords: Expression time course of mouse colon tissue induced by 3% DSS.

Overall design: C57BL/6J mice were given 3% DSS in the drinking water and tissues from individual cohorts were collected at days 0, 2, 4 and 6. Total RNA were extracted from the colon tissue and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.

Background corr dist: KL-Divergence = 0.2821, L1-Distance = 0.0519, L2-Distance = 0.0064, Normal std = 0.2889

1.381 Kernel fit Pairwise Correlations Normal fit

Density 0.691

0.000 CEM 1

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

Pre-normalization Quantiles

normal normalmouse normalcolon,mouse D0M1 normalcolon,mouse (0.0211656) D0M2 normalcolon,mouse (0.0160375) D0M3 coloncolon,mouse (0.0192451)of D0M4 coloncolon, mouse (0.034412)of D0M5colon treatedmouse (0.0288336)ofcolon treatedmousewith ofDSScolon treatedmousewith for ofDSS 2colon treatedmouseday,with for D2M1ofDSS 2colon treatedmouseday,with for (0.0199612) D2M6ofDSS 2colon treatedmouseday,with for (0.0651149) D2M7ofDSS 2colon treatedmouseday,with for (0.0136324) D2M8ofDSS 2colon treatedmouseday,with for (0.0543905) D2M17ofDSS 2colon treatedmouseday,with for (0.0103586)D2M52ofDSS 4colon treatedmouseday,with for (0.0153825)D4M1ofDSS 4colon treatedmouseday,with for (0.0564267) D4M3ofDSS 4colon treatedmouseday,with for (0.00534407) D4M4ofDSS 4colon treatedmouseday,with for (0.0993497) D4M6ofDSS 4colon treatedmouseday,with for (0.0265422) D4M7ofDSS 4colon treatedmouseday,with for (0.00832905) D4M8ofDSS 6colon treatedmouseday,with for (0.0455463) D6M1ofDSS 6 treatedmouseday,with for (0.00809219) D6M3DSS 6 treatedday,with for (0.0525541) D6M4DSS 6 day,with for (0.049675) D6M7DSS 6[ day, min for (0.0156951) D6M21 6 day, ] (0.220693)D6M29 (0.113219)[ medium ] [ max ] CEM 1 Atp2a1 138.2 1281.8 6285.3 P ( S | Z, I ) = 1.00 Ryr1 31.5 274.9 1520.6 Mean Corr = 0.71558 Casq1 89.5 385.8 1233.1 Tcap 101.3 690.3 1778.1 Mypn 23.7 103.2 426.3 Cacna1s 7.1 90.5 274.5 Ttn 2.4 37.7 131.8 Ankrd23 22.9 165.7 590.7 Smtnl1 8.4 94.5 212.5 Aldoa 10524.3 12264.5 15348.0 Actc1 168.2 355.9 964.0 Myl3 95.9 1383.0 3512.2 Ankrd2 4.6 10.8 281.1 Tnnt3 3.0 1356.5 6961.3 Tnni2 9.2 2458.5 9664.4 Tnnc2 6.2 4381.8 11200.0 Myot 42.6 395.0 1891.4 Mylpf 68.6 2182.7 7705.2 CEM 1 + Myl1 68.9 2675.5 10603.6 Top 10 Genes Ckm 719.5 2880.1 12049.4 Acta1 351.9 7560.7 17447.0 Mybpc2 5.3 350.5 3901.0 Ldb3 5.2 289.1 1025.3

Null module Ankrd1 Kat2b GEO Series "GSE28389" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.353

0.000 CEM 1

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

Pre-normalization Quantiles

[E-MTAB-368][E-MTAB-368] Mouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMousestage[E-MTAB-368] E7.5 developmentalMousestage[E-MTAB-368] 1 (0.0370187) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0423371) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.0429252) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0416125) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0397234) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0310516) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0103081) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.0164663) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0169121) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0165274) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0121461) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0123107) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0173378) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0148904) developmentalMousestage 1 E14.5 (0.0151328) developmentalMousestage 2 E16.5 (0.014191) developmentalstage 1 E16.5(0.029432) stage[ min 2 E18.5(0.0285263) stage 1] E18.5(0.263013) 2 (0.298137)[ medium ] [ max ] CEM 1 Atp2a1 53.6 204.2 6214.9 P ( S | Z, I ) = 1.00 Ryr1 2.2 45.3 809.7 Mean Corr = 0.71425 Casq1 76.6 252.4 5370.2 Tcap 38.4 132.1 1854.1 Mypn 1.3 36.5 806.2 Cacna1s 4.3 38.3 403.8 Ttn 4.6 37.0 276.5 Ankrd23 6.7 80.8 379.8 Smtnl1 2.6 32.9 870.9 Aldoa 5253.0 15352.7 21382.0 Actc1 260.7 15765.7 27244.5 Myl3 45.5 984.8 1616.5 Ankrd2 8.0 60.9 354.6 Tnnt3 20.3 72.9 17818.1 Tnni2 2.5 95.4 22118.8 Tnnc2 7.0 540.7 27124.3 Myot 1.7 39.1 7442.2 Mylpf 63.5 1098.0 30425.9 CEM 1 + Myl1 4.4 1088.5 30189.5 Top 10 Genes Ckm 6.5 43.1 24316.7 Acta1 163.0 1481.4 34998.3 Mybpc2 1.5 7.4 1145.4 Ldb3 4.2 92.4 3817.7

Null module Ankrd1 Kat2b GEO Series "GSE19079" 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=GSE19079 Status: Public on Nov 19 2010 Title: Myocardial expression data from wild-type and akt2-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Wild-type (WT) C57Bl/6 and akt2-/- male mice.

Keywords: RNA Expression Array

Overall design: Left ventricles (LV) from 12-16 week-old male wild type mice and age-matched akt2-/- mice

Background corr dist: KL-Divergence = 0.0153, L1-Distance = 0.0204, L2-Distance = 0.0006, Normal std = 0.7977

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

Mouse LV,Mouse akt2-/- LV,Mouse 1 WT (0.174336) LV,Mouse1 (0.459694) WT LV,Mouse2 (0.153882) WT LV,Mouse3 (0.0905151) akt2-/- LV, 2 akt2-/- (0.0743775) 3 (0.0471954)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 43.2 97.4 236.3 P ( S | Z, I ) = 1.00 Ryr1 3.0 7.1 24.8 Mean Corr = 0.71399 Casq1 207.2 685.0 996.3 Tcap 24376.8 32895.0 37800.6 Mypn 3046.7 3693.2 4551.8 Cacna1s 134.9 229.5 409.7 Ttn 886.8 960.5 2295.0 Ankrd23 6330.6 7068.2 9954.2 Smtnl1 3.1 9.7 89.6 Aldoa 30239.0 35036.8 64045.2 Actc1 56121.3 79985.3 190856.4 Myl3 40987.4 59861.4 163923.5 Ankrd2 4.7 14.3 38.3 Tnnt3 4.5 9.3 122.1 Tnni2 31.0 97.1 293.0 Tnnc2 8.7 34.0 152.7 Myot 2794.0 4797.9 6124.3 Mylpf 97.7 165.7 447.7 CEM 1 + Myl1 1698.5 4867.8 7609.7 Top 10 Genes Ckm 44377.1 53816.0 64104.3 Acta1 9523.5 13209.0 19973.3 Mybpc2 312.5 421.8 993.5 Ldb3 18860.4 25448.2 29093.4

Null module Ankrd1 Kat2b GEO Series "GSE16992" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 48 -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=GSE16992 Status: Public on Mar 21 2012 Title: Expression Profiling of Early Myogenesis - Affymetrix Dataset Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22147266 Summary & Design: Summary: Analysis of Early Myogenesis Reveals an Extensive Set of Transcriptional Regulators Whose Knock-down Can Inhibit Differentiation

Myogenesis is a tightly controlled process involving the transcriptional activation and repression of thousands of genes. Although many components of the transcriptional network are known for the later phases of myogenesis, relatively little work has described the transcriptional landscape within the first 24 hours, when myoblasts commit to differentiate. Through dense temporal sampling of differentiating C2C12 myoblasts, we identify 266 transcriptional regulators (TRs) whose expression is altered within the first 12 hours of myogenesis. A high-content shRNA screen of 76 TRs involving 427 stable lines identified 48 genes whose knockdown significantly inhibits differentiation of C2C12 myoblasts. These include known regulators of myogenesis (Myod1, Myog and Myf5), as well as 26 regulators not previously associated with the process. Of the TRs differentially expressed within the first 24 hours, two-thirds inhibited differentiation when knocked down. Surprisingly, a similar proportion (67%) of shRNAs targeting TRs whose expression did not change during differentiation also inhibited myogenesis, suggesting that both stably and differentially expressed TRs are essential for this complex differentiation program. This implies that microarray-based approaches that concentrate functional validation studies on differentially-expressed genes will fail to identify many genes that are critically implicated in complex biological processes.

Overall design: C2C12 myoblasts were differentiated into myotubes and sampled at various timepoints for gene expression measurement on MOE-430v2 chips. Cells grown in separate plates were harvested at 14 different timepoints: t_-24h, t_0h, t_0.5h, t_1h, t_1.5h, t_2h, t_3h, t_6h, t_9h, t_12h, t_24h, t_48h, t_96h, t_144h. Cells were also pre-treated with 50uM cycloheximide 1 hour prior to inducing differentiation and harvested at two timepoints: t_chx_1h, t_chx_3h. All harvests were performed in triplicate using growths from successive passages.

Background corr dist: KL-Divergence = 0.1939, L1-Distance = 0.0505, L2-Distance = 0.0065, Normal std = 0.3363

1.186 Kernel fit Pairwise Correlations Normal fit

Density 0.593

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_-24hr_ctrl_rep1C2C12_-24hr_ctrl_rep2C2C12_-24hr_ctrl_rep3C2C12_0hr_ctrl_rep1 (0.0111326)C2C12_0hr_ctrl_rep2 (0.0101604)C2C12_0hr_ctrl_rep3 (0.0159785) (0.00493453)C2C12_0.5hr_differentiation_rep1 (0.00612256)C2C12_0.5hr_differentiation_rep2 (0.00793683)C2C12_0.5hr_differentiation_rep3C2C12_1hr_differentiation_rep1C2C12_1hr_differentiation_rep2 (0.00438917)C2C12_1hr_differentiation_rep3 (0.00852577)C2C12_1.5hr_differentiation_rep1 (0.0061368)C2C12_1.5hr_differentiation_rep2 (0.00395657)C2C12_1.5hr_differentiation_rep3 (0.0206415)C2C12_2hr_differentiation_rep1 (0.00987677)C2C12_2hr_differentiation_rep2 (0.0089442)C2C12_2hr_differentiation_rep3 (0.00893284)C2C12_3hr_differentiation_rep1 (0.00849657)C2C12_3hr_differentiation_rep2 (0.00436265)C2C12_3hr_differentiation_rep3 (0.00579401)C2C12_6hr_differentiation_rep1 (0.00658724)C2C12_6hr_differentiation_rep2 (0.010833)C2C12_6hr_differentiation_rep3 (0.00691784)C2C12_9hr_differentiation_rep1 (0.00763474)C2C12_9hr_differentiation_rep2 (0.00418088)C2C12_9hr_differentiation_rep3 (0.00555966)C2C12_12hr_differentiation_rep1 (0.00490134)C2C12_12hr_differentiation_rep2 (0.00356467)C2C12_12hr_differentiation_rep3 (0.0054768)C2C12_24hr_differentiation_rep1 (0.0091763)C2C12_24hr_differentiation_rep2 (0.00611822)C2C12_24hr_differentiation_rep3 (0.00348562)C2C12_48hr_differentiation_rep1 (0.005833)C2C12_48hr_differentiation_rep2 (0.0178657)C2C12_48hr_differentiation_rep3 (0.00759959)C2C12_96hr_differentiation_rep1 (0.0053168)C2C12_96hr_differentiation_rep2 (0.0312175)C2C12_96hr_differentiation_rep3 (0.0385896)C2C12_144hr_differentiation_rep1 (0.0236884)C2C12_144hr_differentiation_rep2 (0.112982)C2C12_144hr_differentiation_rep3 (0.0900566)C2C12_1hr_CHX_rep1 (0.0198902)C2C12_1hr_CHX_rep2 (0.159559)C2C12_1hr_CHX_rep3 (0.0963786) C2C12_3hr_CHX_rep1(0.0199541) (0.0593881) C2C12_3hr_CHX_rep2(0.0195074) C2C12_3hr_CHX_rep3(0.0118129) (0.0176354) (0.0170515) (0.0249145)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 103.5 655.1 12064.1 P ( S | Z, I ) = 1.00 Ryr1 40.1 163.9 3348.3 Mean Corr = 0.71132 Casq1 52.0 64.6 4745.9 Tcap 74.8 121.4 6287.4 Mypn 43.5 63.0 1483.8 Cacna1s 44.7 62.3 1973.4 Ttn 43.4 66.8 284.5 Ankrd23 88.9 131.3 3213.1 Smtnl1 50.5 60.7 82.7 Aldoa 8841.3 16431.0 28577.2 Actc1 134.3 10877.1 51719.9 Myl3 104.1 128.9 213.0 Ankrd2 88.0 157.0 6660.6 Tnnt3 97.0 906.1 30740.2 Tnni2 149.5 1727.6 52829.2 Tnnc2 65.6 3770.2 47383.7 Myot 29.9 38.9 3354.7 Mylpf 241.5 12023.7 80414.2 CEM 1 + Myl1 217.6 9930.4 79255.0 Top 10 Genes Ckm 97.6 402.4 16777.5 Acta1 328.8 9666.3 80498.5 Mybpc2 47.2 63.5 560.1 Ldb3 83.6 184.6 3761.7

Null module Ankrd1 Kat2b GEO Series "GSE6055" 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=GSE6055 Status: Public on Dec 14 2006 Title: Gene Expression Profiling Reveals Unique Pathways Associated with Differential Severity of Lyme Arthritis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17114465 Summary & Design: Summary: Keywords: disease state analysis, time course

Overall design: Expression profiling of ankle tissues of C3H, C57BL/6, and C57BL/6-IL10-/- mice infected with B. burgdorfer (0, 1, 2, and 4 weeks post-infection)

Background corr dist: KL-Divergence = 0.0594, L1-Distance = 0.0221, L2-Distance = 0.0005, Normal std = 0.5419

0.744 Kernel fit Pairwise Correlations Normal fit

Density 0.372

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

ExpressionExpression dataExpression from data ankleExpression from data tissue ankleExpression from dataof tissue ankleExpressionC57BL/6 from dataof tissue ankleExpressionC57BL/6 micefrom dataof tissue atankleExpressionC57BL/6 micefrom0 week dataof tissue atankleC57BL/6 micefrom1of week datainfectionof tissue atankleC57BL/6 micefrom2of week infectionof tissue (uninfected) atankleC57BL/6 IL10KO4of week infectionof tissue (0.0996224) C57BL/6[ IL10KOofmicemin (0.0782398) infectionof (0.0199007) C57BL/6at IL10KO mice0 week] (0.0474456) at IL10KO mice1of week infection at mice2of[ week infectionmedium (uninfected)at 4of week infection (0.101606) of (0.0839718)infection (0.195059) ] (0.374154)[ max ] CEM 1 Atp2a1 24299.4 39248.5 45954.9 P ( S | Z, I ) = 1.00 Ryr1 8857.5 18741.9 20594.4 Mean Corr = 0.70837 Casq1 12515.1 22737.9 26692.1 Tcap 14464.2 26505.5 28011.5 Mypn 2483.3 6877.6 8230.6 Cacna1s 2092.9 6677.0 7955.7 Ttn 686.9 1890.0 2532.5 Ankrd23 1551.4 5576.2 6068.9 Smtnl1 2459.0 9120.2 10977.6 Aldoa 25584.9 39644.4 45789.0 Actc1 2290.1 6378.7 9920.0 Myl3 1971.9 7078.3 9433.3 Ankrd2 658.5 3468.2 5450.0 Tnnt3 28638.3 44110.0 51627.5 Tnni2 26597.4 41578.3 47593.9 Tnnc2 24918.8 33774.3 39003.1 Myot 8998.2 23072.8 25298.6 Mylpf 19535.0 31291.3 40180.8 CEM 1 + Myl1 26309.6 37319.5 45930.3 Top 10 Genes Ckm 28465.6 38862.6 45854.7 Acta1 29741.5 41994.5 49786.2 Mybpc2 9986.4 13188.7 15983.0 Ldb3 6488.7 14537.1 20646.3

Null module Ankrd1 Kat2b GEO Series "GSE41342" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 26 -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=GSE41342 Status: Public on Nov 01 2012 Title: Data from a time course study of gene expression in a mouse model of osteoarthritis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23382930 Summary & Design: Summary: The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint organ and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained.

Overall design: RNA was pooled prior to microarray analysis such that 3 randomly selected samples from each surgical group and time point were pooled to create each biological replicate. Because 9 mice were used for each experimental group, a total of three biological replicates per group were analyzed using the Affymetrix Mouse Genome 430 2.0 oligonucleotide arrays as described. One replicate pool, which was from week two DMM mice, did not meet the RNA integrity level needed for microarray analysis; thus, this pool was not analyzed further, leaving two pools for the week two DMM mice.

Background corr dist: KL-Divergence = 0.1052, L1-Distance = 0.0242, L2-Distance = 0.0007, Normal std = 0.4325

0.922 Kernel fit Pairwise Correlations Normal fit

Density 0.461

0.000 CEM 1

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

Pre-normalization Quantiles

Joint tissue-timeJoint tissue-timeJoint 0-replicate tissue-timeJoint 0-replicate tissue-time1 Joint(0.044964) 0-replicate tissue-time2 Joint(0.0315028) 2 weeks-sham-replicate tissue-time3 Joint(0.0282576) 2 weeks-sham-replicate tissue-timeJoint 2 weeks-sham-replicate tissue-timeJoint 4 weeks-sham-replicate1 tissue-time(0.152371)Joint 4 weeks-sham-replicate2 tissue-time(0.0497141)Joint 4 weeks-sham-replicate3 tissue-time(0.0768563)Joint 8 weeks-sham-replicate1 tissue-time(0.0105662)Joint 8 weeks-sham-replicate2 tissue-time(0.00924775)Joint 8 weeks-sham-replicate3 tissue-time(0.0139923)Joint 16 1 weeks-sham-replicate tissue-time(0.14533)Joint 16 2 weeks-sham-replicate tissue-time(0.0517293)Joint 16 3 weeks-sham-replicate tissue-time(0.00989746)Joint 2 weeks-DMM-replicate 1tissue-time (0.0328326)Joint 2 weeks-DMM-replicate 2tissue-time (0.0172878)Joint 4 weeks-DMM-replicate 3tissue-time (0.0324496)Joint 4 2weeks-DMM-replicate (0.025345)tissue-timeJoint 4 3weeks-DMM-replicate (0.0342659)tissue-timeJoint 8 1weeks-DMM-replicate (0.00938906)tissue-timeJoint 8 2weeks-DMM-replicate (0.0291335)tissue-timeJoint 8 3weeks-DMM-replicate (0.0187633)tissue-timeJoint 16 1 weeks-DMM-replicate(0.024062)tissue-time 16 2 weeks-DMM-replicate(0.0123171) 16 3 weeks-DMM-replicate(0.00366432) 1 (0.117721)[ min 2 (0.00898021) ]3 (0.00935982)[ medium ] [ max ] CEM 1 Atp2a1 442.1 3021.8 6571.2 P ( S | Z, I ) = 1.00 Ryr1 127.0 505.2 1148.3 Mean Corr = 0.70464 Casq1 422.7 1323.5 2717.9 Tcap 338.1 1136.0 3103.5 Mypn 122.6 289.7 524.8 Cacna1s 99.2 170.0 311.6 Ttn 68.2 133.0 230.8 Ankrd23 269.4 709.5 1763.1 Smtnl1 107.3 162.6 302.6 Aldoa 7839.9 11056.5 16876.8 Actc1 445.3 648.9 1277.9 Myl3 218.8 264.0 482.2 Ankrd2 149.5 183.3 287.8 Tnnt3 583.0 4091.9 9268.8 Tnni2 993.2 6060.0 12991.3 Tnnc2 1321.8 8572.6 16900.3 Myot 166.2 1060.9 3117.0 Mylpf 1241.9 6425.5 13384.0 CEM 1 + Myl1 1289.4 6547.5 13999.0 Top 10 Genes Ckm 771.2 5925.9 12569.7 Acta1 1123.4 8014.5 17019.9 Mybpc2 187.3 1432.9 3344.3 Ldb3 228.2 821.0 1613.3

Null module Ankrd1 Kat2b GEO Series "GSE5800" 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=GSE5800 Status: Public on Oct 01 2006 Title: Expression data from mouse IRF6 null and wt skin Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17041601 Summary & Design: Summary: Transcription factor paralogs may share a common role (e.g. Hox) in staged or overlapping expression in specific tissues. In other examples, members have distinct roles in a range of embryologic, differentiation or response pathways (e.g. Tbx, Pax). For the Interferon Regulatory Factor (IRF) family of transcription factors, mice deficient in Irf1, Irf2, Irf3, Irf4, Irf5, Irf7, Irf8 or Irf9, have defects in the immune response but display no embryologic abnormalities. Mice deficient for Irf6 have not been reported, but in humans, mutations in IRF6 cause two Mendelian orofacial clefting syndrome, and genetic variation in IRF6 confers risk for isolated cleft lip and palate.

Mice deficient for Irf6 have abnormal skin, limb and craniofacial development. Histological and gene expression analyses indicate that the primary defect is in keratinocyte differentiation and proliferation. This study describes a novel role for an IRF family member in epidermal development.

Keywords: Comparison of tissue from two genotypes

Overall design: Skin from E17.5 mice was removed and flash frozen for RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.0385, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.6252

0.647 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

IRF6 knockout,IRF6 knockout,IRF6 biological knockout,IRF6 biological rep1 wt,IRF6 biologicalbiological(0.110681) rep2 wt,IRF6 biological(0.178992) rep3rep1 wt, biological(0.151451)(0.108938) rep2 (0.105352) rep3 (0.344585)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 2716.4 4399.4 6170.4 P ( S | Z, I ) = 1.00 Ryr1 583.4 1156.6 1501.2 Mean Corr = 0.70027 Casq1 1419.4 2161.8 2904.7 Tcap 292.4 380.5 619.6 Mypn 632.1 1003.8 1378.4 Cacna1s 161.8 309.9 468.8 Ttn 171.5 301.8 381.1 Ankrd23 107.5 176.0 350.6 Smtnl1 311.1 441.8 831.1 Aldoa 16442.5 18244.3 19588.7 Actc1 19259.6 25253.9 27195.2 Myl3 395.8 681.8 880.0 Ankrd2 81.4 250.9 340.7 Tnnt3 6697.4 10176.0 10778.6 Tnni2 9574.1 13377.0 15578.5 Tnnc2 14795.7 19427.3 23837.6 Myot 1797.7 2525.6 3575.8 Mylpf 15651.4 20566.3 24335.6 CEM 1 + Myl1 21259.0 29186.7 30676.7 Top 10 Genes Ckm 11739.9 16021.6 18976.5 Acta1 23936.8 32211.7 33493.6 Mybpc2 232.2 403.0 668.6 Ldb3 1348.2 1957.5 2850.0

Null module Ankrd1 Kat2b GEO Series "GSE36826" 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=GSE36826 Status: Public on Dec 05 2012 Title: Neutrophil-derived IL-1Î² is sufficient for abscess formation in immunity against Staphylococcus aureus in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23209417 Summary & Design: Summary: Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils.

Overall design: Lesional skin biopsies obtained from C57BL/6J WT mice or IL-1R-deficient mice at 4 hours post-infection with Staphylococcus aureus. Uninfected skin biopsies were also collected from WT and IL-1R-deficient mice.

Background corr dist: KL-Divergence = 0.0935, L1-Distance = 0.0346, L2-Distance = 0.0023, Normal std = 0.4518

0.883 Kernel fit Pairwise Correlations Normal fit

Density 0.442

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_0hr-rep1WT_0hr-rep2 (0.0972241)WT_0hr-rep3 (0.056208)WT_4hr-rep1 (0.066831)WT_4hr-rep2 (0.0454247)WT_4hr-rep3 (0.0341063)IL-1Rko_0hr-rep1 (0.074037)IL-1Rko_0hr-rep2IL-1Rko_0hr-rep3 (0.037879)IL-1Rko_4hr-rep1 (0.0268566)IL-1Rko_4hr-rep2 (0.322692)IL-1Rko_4hr-rep3 (0.144535) (0.0775546) (0.0166511) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 28277.6 62120.7 92566.0 P ( S | Z, I ) = 1.00 Ryr1 4114.6 10962.1 28584.6 Mean Corr = 0.68482 Casq1 7083.1 16878.4 36848.6 Tcap 4354.7 11534.5 31576.2 Mypn 1270.2 3208.2 7898.6 Cacna1s 984.8 2618.4 6725.1 Ttn 294.8 1074.2 2446.8 Ankrd23 968.4 6349.7 17029.2 Smtnl1 635.0 1026.6 1696.5 Aldoa 34831.5 59286.2 87393.3 Actc1 371.2 1901.1 35067.4 Myl3 292.0 512.4 2391.8 Ankrd2 693.5 1937.7 7375.3 Tnnt3 26090.8 55303.4 89745.6 Tnni2 30995.0 60387.6 99425.6 Tnnc2 35132.6 53332.1 77074.5 Myot 4579.1 12216.5 29322.1 Mylpf 33282.7 53870.8 87853.4 CEM 1 + Myl1 30663.6 54110.1 81624.7 Top 10 Genes Ckm 32927.3 66280.5 97599.4 Acta1 61027.1 80811.5 104807.3 Mybpc2 6853.4 21086.2 57184.9 Ldb3 3624.6 9073.0 23014.2

Null module Ankrd1 Kat2b GEO Series "GSE19517" 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=GSE19517 Status: Public on Mar 01 2010 Title: Gene expression profiling of conditional ablation of Indian hedgehog in the mouse uterus Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20056671 Summary & Design: Summary: Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling.

Keywords: two group comparison

Overall design: We conditionally ablated Indian hedgehog in the mouse uterus using the PRcre mouse model (PRcre/+Ihhf/f; Ihhd/d). High density DNA microarray analysis was performed on Day -1 of the artificial decidual response on Ihhf/f and Ihhd/d uteri.

Background corr dist: KL-Divergence = 0.0158, L1-Distance = 0.0218, L2-Distance = 0.0006, Normal std = 0.7834

0.509 Kernel fit Pairwise Correlations Normal fit

Density 0.255

0.000 CEM 1

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

Pre-normalization Quantiles

Ihhf/f, ReplicateIhhf/f, ReplicateIhhf/f, 1 (0.0916042) ReplicateIhhd/d, 2 (0.198276) Ihhd/d,Replicate 3 (0.494442) Ihhd/d,Replicate 1 (0.0488119) Replicate 2 (0.0722924) 3 (0.0945737)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 220.1 247.3 1843.8 P ( S | Z, I ) = 1.00 Ryr1 93.0 113.4 412.7 Mean Corr = 0.67647 Casq1 323.6 360.5 842.4 Tcap 151.3 165.4 570.0 Mypn 89.3 110.9 200.9 Cacna1s 122.0 146.2 235.7 Ttn 78.7 92.3 144.6 Ankrd23 259.3 300.4 431.0 Smtnl1 179.7 219.8 250.2 Aldoa 4246.9 5138.6 6937.8 Actc1 164.1 213.6 332.7 Myl3 256.8 308.9 400.8 Ankrd2 167.4 212.6 246.8 Tnnt3 202.7 238.1 2065.5 Tnni2 574.1 1090.6 3044.8 Tnnc2 96.3 307.5 4172.5 Myot 57.5 67.8 335.1 Mylpf 145.7 170.7 4125.1 CEM 1 + Myl1 80.8 105.4 3981.1 Top 10 Genes Ckm 235.9 361.2 2991.5 Acta1 2294.9 6868.9 10896.4 Mybpc2 116.8 148.0 953.3 Ldb3 233.1 256.6 439.0

Null module Ankrd1 Kat2b GEO Series "GSE10246" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 182 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

Details of this dataset are not shown due to large number of samples and the page size limit. Find details in http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10246

Background corr dist: KL-Divergence = 0.5414, L1-Distance = 0.1198, L2-Distance = 0.0520, Normal std = 0.2635 GEO Series "GSE3501" 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=GSE3501 Status: Public on Jan 01 2006 Title: Comparative analysis of 10 week and 5 week Bitransgenic mice (LH mouse crossed with MMTV-neu mouse) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16434967 Summary & Design: Summary: To identify genes that may facilitate early steps of ErbB2/Neu-mediated mammary tumorigenesis, we performed comparative microarray analysis of 5- and 10-week bitransgenic mammary glands (LHxMMTV-neu) in triplicate.

Keywords: transgenic mouse, erbB2, MMTV-neu, HER2, mammary tumor, breast cancer

Overall design: We analyzed 3 pooled RNA samples that represented 3 animals for each time point so that a total of 9 bitransgenic mice were analyzed per time point.

Background corr dist: KL-Divergence = 0.0235, L1-Distance = 0.0195, L2-Distance = 0.0004, Normal std = 0.7222

0.562 Kernel fit Pairwise Correlations Normal fit

Density 0.281

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

10week10week bitransgenic10week bitransgenic Ker825 bitransgenic week (0.220095) Ker83 5bitransgenic week (0.0656945) Ker4 5bitransgenic week (0.0828827) Ker85 bitransgenic (0.131538) Ker86 (0.0915297) Ker87 (0.40826)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 835.5 9538.8 14492.2 P ( S | Z, I ) = 1.00 Ryr1 139.3 1448.5 4979.8 Mean Corr = 0.67609 Casq1 275.9 2732.3 7044.8 Tcap 405.9 2611.4 5963.3 Mypn 16.9 333.8 1580.3 Cacna1s 122.4 401.0 1423.4 Ttn 11.6 159.4 442.6 Ankrd23 54.8 483.8 1699.7 Smtnl1 9.9 161.9 795.5 Aldoa 6881.1 12800.6 14429.5 Actc1 144.8 253.5 537.1 Myl3 185.9 292.2 393.3 Ankrd2 79.9 201.1 263.7 Tnnt3 408.2 4619.9 12274.9 Tnni2 518.4 5659.7 13478.5 Tnnc2 731.3 9763.0 13694.0 Myot 138.5 1506.9 5351.9 Mylpf 374.9 5539.3 12661.5 CEM 1 + Myl1 569.7 11486.9 12590.7 Top 10 Genes Ckm 689.9 10591.3 16291.6 Acta1 2665.1 12767.1 16301.0 Mybpc2 133.0 2320.4 7522.4 Ldb3 153.8 1108.5 4744.8

Null module Ankrd1 Kat2b GEO Series "GSE31004" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31004 Status: Public on Dec 15 2011 Title: Effects of Nicotine on the Fetal Mouse Palate Development and Transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus. To demonstrate the effect of nicotine on craniofacial development, particularly palatogenesis, we delivered three different doses of nicotine (1.5, 3.0 and 4.5 mg/kg/day) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous osmotic mini-pump. We assessed the pups for morphological anomalies, as well as genome-wide mRNA (transcriptome) microarray analysis. Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality in the pups. However, it did not cause obvious cleft palate. The microarray data analysis using IPA identified differential expression of genes involved in various biological pathways, particularly cancer, genetic diseases, and tissue development in response to consistent nicotine exposure. 6232 up-regulated and 6310 down-regulated genes were detected in nicotine-treated groups compared to the control. Moreover, 45% of the genes associated with cleft palate were found to be affected by nicotine. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and RT-PCR. We concluded that consistent nicotine exposure during pregnancy interferes with normal growth and development of the fetus including palatogenesis; however, this interference does not result in cleft palate, rather smaller palate size with persistent MES. To our knowledge, this is the first experiment revealing the impact of nicotine on the fetal palate transcriptome in mice.

Overall design: Total 8 samples were analyzed. Using an osmotic minipump, duplicate samples from palates of either sterile physiological saline or nicotine (1.5 mg/kg/day, 3.0 mg/kg/day, or 4.5 mg/kg/day)-treated newborn pups.

Background corr dist: KL-Divergence = 0.0673, L1-Distance = 0.0308, L2-Distance = 0.0016, Normal std = 0.5256

0.759 Kernel fit Pairwise Correlations Normal fit

Density 0.379

0.000 CEM 1

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

Pre-normalization Quantiles

Saline control,Saline control, Nicbiological 1.5mg/kg/day, Nicbiological rep1 1.5mg/kg/day,Nic (0.144837) rep2 biological3.0mg/kg/day,Nic (0.275841) biological3.0mg/kg/day, rep1Nic biological4.5mg/kg/day,(0.0425677) rep2Nic biological4.5mg/kg/day,(0.179285) rep1 biological(0.068927) rep2 biological(0.0159403) rep1 (0.0848339) rep2[ min (0.187769) ] [ medium ] [ max ] CEM 1 Atp2a1 8475.6 19966.9 23810.9 P ( S | Z, I ) = 1.00 Ryr1 1623.5 6074.3 6415.6 Mean Corr = 0.67562 Casq1 4352.5 11647.3 13202.9 Tcap 1158.5 5019.4 12531.0 Mypn 779.1 4321.7 5177.1 Cacna1s 427.3 1687.0 2042.5 Ttn 288.1 1214.2 1616.4 Ankrd23 252.2 668.8 1207.4 Smtnl1 248.7 918.3 1220.1 Aldoa 11496.2 26381.4 30020.0 Actc1 13466.3 28868.0 32017.4 Myl3 413.4 1475.3 8807.9 Ankrd2 2557.2 3269.6 15810.2 Tnnt3 11368.6 24616.1 30541.8 Tnni2 12240.8 29629.4 36637.0 Tnnc2 17337.5 29543.5 31550.3 Myot 5185.3 14200.2 21203.4 Mylpf 21377.4 38386.2 42859.6 CEM 1 + Myl1 21426.9 34703.4 37575.0 Top 10 Genes Ckm 15178.1 33869.5 38547.0 Acta1 32780.0 41351.5 44910.3 Mybpc2 2193.0 6073.1 8339.0 Ldb3 2675.6 10750.8 13355.3

Null module Ankrd1 Kat2b GEO Series "GSE43242" 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=GSE43242 Status: Public on Jan 21 2014 Title: Effect of osteoblast-specific constitutive activation of beta-catenin or deletion of FoxO1 on gene expression in mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24429522 Summary & Design: Summary: The gene expression of mice with osteoblast-specific beta-catenin activation or FoxO1 deactivation are each compared to that of Wt.

Overall design: C. Osteoblast specific FoxO1 deleted mice (n=3)

Background corr dist: KL-Divergence = 0.1216, L1-Distance = 0.0309, L2-Distance = 0.0017, Normal std = 0.4052

0.985 Kernel fit Pairwise Correlations Normal fit

Density 0.492

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

a.wt.1 (0.118959)a.wt.2 (0.139738)a.wt.3 (0.0384728)a.wt.4 (0.0462796)b.bcat.1b.bcat.2 (0.0623167)b.bcat.3 (0.134296)c.FoxO1.1 (0.0342941)c.FoxO1.2 (0.284743)c.FoxO1.3 (0.078345) (0.0625553) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 1109.9 2657.7 4472.4 P ( S | Z, I ) = 1.00 Ryr1 479.8 1283.6 1854.5 Mean Corr = 0.67479 Casq1 1125.2 2219.4 3228.9 Tcap 376.4 1028.9 2144.3 Mypn 287.3 727.2 1072.5 Cacna1s 150.8 240.0 363.5 Ttn 135.9 255.3 366.2 Ankrd23 161.6 358.5 678.5 Smtnl1 86.0 310.0 707.4 Aldoa 9193.2 12299.0 14728.3 Actc1 889.2 6500.3 12737.8 Myl3 61.2 403.4 611.5 Ankrd2 133.1 486.4 2014.6 Tnnt3 3973.7 8056.7 11967.5 Tnni2 5427.0 12730.3 16691.5 Tnnc2 10557.3 17516.7 23442.3 Myot 1222.8 3706.9 5619.8 Mylpf 12818.6 23106.0 33383.1 CEM 1 + Myl1 15781.5 27674.1 34084.5 Top 10 Genes Ckm 2829.4 7890.9 11884.8 Acta1 19700.6 31789.2 36785.0 Mybpc2 162.7 476.5 835.4 Ldb3 582.6 1658.9 2909.0

Null module Ankrd1 Kat2b GEO Series "GSE11186" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 33 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11186 Status: Public on Jul 17 2009 Title: Expression profiling of mouse dorsal skin during hair follicle cycling Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19629164 Summary & Design: Summary: Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.

Overall design: To investigate the molecular control of hair follicle cycling, we profiled mRNA expression in mouse dorsal skin at multiple representative time points in the synchronized second postnatal hair growth cycle and in a depilation-induced hair growth cycle. For profiling of second synchronized and depilation-induced hair growth cycle, the same upper-mid region of dorsal skin was excised from C57BL/6 mice at representative postnatal days (P). The time points for second hair growth cycle are classified into different phases of the hair growth cycle based on established morphological guidelines as follow: early anagen (P23, P25), mid anagen (P27), late anagen (P29, P34), early catagen (P37, P39), mid catagen (P41), and telogen (P44). Depilation-induced hair growth cycle by applying wax/rosin mixture on the dorsal skin of seven-week old mice (all follicles in telogen) was performed on mice. The corresponding phases of the hair growth cycle at number of days following depilation (D) is as follow: early anagen (D3), mid anagen (D5), late anagen (D8, D12), and early catagen (D17). For each time point, multiple biological replicates were profiled, with each mouse dorsal skin separately hybridized to an Affymetrix array.

Background corr dist: KL-Divergence = 0.2054, L1-Distance = 0.0354, L2-Distance = 0.0025, Normal std = 0.3341

1.194 Kernel fit Pairwise Correlations Normal fit

Density 0.597

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 dorsalWT skindorsalWT at P23, skindorsalWT biologicalat P23, skindorsalWT biologicalat P25,skinreplicatedorsalWT biologicalat P25,skinreplicatedorsal 1 (0.0233369)WT biologicalat P27,skinreplicatedorsal 2 (0.00699838)WT biologicalat P27,skinreplicatedorsal 1 (0.0109969)WT biologicalat P27,skinreplicatedorsal 2 (0.00942079)WT biologicalat P29,skinreplicatedorsal 1 (0.0124645)WT biologicalat P29,skinreplicatedorsal 2 (0.0120119)WT biologicalat P29,skinreplicatedorsal 3 (0.00898818)WT biologicalat P34,skinreplicatedorsal 1 (0.00744364)WT biologicalat P37,skinreplicatedorsal 2 (0.0172222)WT biologicalat P37,skinreplicatedorsal 3 (0.0202724)WT biologicalat P37,skinreplicatedorsal 1 (0.0148476)WT biologicalat P39,skinreplicatedorsal 1 (0.00990522)WT biologicalat P39,skinreplicatedorsal 2 (0.00686885)WT biologicalat P39,skinreplicatedorsal 3 (0.0133546)WT biologicalat P41,skinreplicatedorsal 1 (0.0156927)WT biologicalat P41,skinreplicatedorsal 2 (0.0291904)WT biologicalat P41,skinreplicatedorsal 3 (0.0151542)WT biologicalat P44,skinreplicatedorsal 1 (0.00396832)WT biologicalat P44,skinreplicatedorsal 2 (0.00328923)WT biologicalat P44,skinreplicatedorsal 3 (0.00731913)WT biologicalat D3,skinreplicatedorsal 1 biological(0.0490428)WT at D3,skinreplicatedorsal 2 biological(0.0662892)WT at replicate D5, skindorsal 3 biological(0.0511994)WT at replicate D5, skin dorsal1 (0.314555) biologicalWT at replicate D8, skin dorsal2 (0.0628825) biologicalWT at replicate D8, skin dorsal1 (0.131211) biologicalWT at replicate D12, skin dorsal2 (0.0106708)WT atbiological replicate D12, skin dorsal1 (0.0108709) atbiological D17,skinreplicate 2 (0.00871998) atbiological D17,replicate 1 (0.0174012) biological replicate 2 (0.0111735)[ min replicate 1 (0.013401) ] 2 (0.00383569)[ medium ] [ max ] CEM 1 Atp2a1 11120.0 16985.8 45222.8 P ( S | Z, I ) = 1.00 Ryr1 1156.0 2881.9 17685.2 Mean Corr = 0.67248 Casq1 1732.6 6027.2 22838.9 Tcap 1140.6 3293.4 23456.5 Mypn 303.9 888.1 5601.8 Cacna1s 304.5 570.7 3889.6 Ttn 119.7 290.0 1700.4 Ankrd23 487.3 1131.8 6678.2 Smtnl1 189.4 458.4 4885.9 Aldoa 15604.1 22119.7 47032.2 Actc1 234.6 1235.8 9807.2 Myl3 79.4 126.9 189.4 Ankrd2 83.6 291.1 6335.6 Tnnt3 6978.7 15480.8 47455.0 Tnni2 9201.8 18746.8 54264.9 Tnnc2 12929.5 19166.0 39195.5 Myot 1531.0 3493.8 23095.4 Mylpf 8273.8 17307.9 41512.4 CEM 1 + Myl1 15129.1 24932.2 41023.0 Top 10 Genes Ckm 11985.7 20961.3 49505.8 Acta1 21344.6 28210.2 48845.3 Mybpc2 2298.3 5983.8 30231.8 Ldb3 1043.5 2819.6 19416.5

Null module Ankrd1 Kat2b 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 (0.201088)C2C12-day2 (0.119723)C2C12-day4 (0.077035)C2C12-control-day0 (0.419197)C2C12-shRp58-day0 (0.0853026) (0.0976544)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 267.8 3614.8 8578.3 P ( S | Z, I ) = 1.00 Ryr1 251.9 3191.3 6610.9 Mean Corr = 0.67062 Casq1 335.2 936.5 7638.8 Tcap 190.9 275.4 1956.4 Mypn 98.9 188.7 993.8 Cacna1s 102.5 729.4 2852.7 Ttn 85.8 219.3 525.2 Ankrd23 160.5 559.4 2882.0 Smtnl1 49.4 64.3 71.9 Aldoa 6771.2 11386.2 13539.9 Actc1 1175.9 13009.6 14713.3 Myl3 142.0 165.9 180.8 Ankrd2 242.0 2037.6 3386.2 Tnnt3 142.3 6304.9 13949.7 Tnni2 207.3 6658.2 13531.5 Tnnc2 428.9 13774.4 16548.9 Myot 27.8 36.1 159.6 Mylpf 784.3 16680.2 18282.1 CEM 1 + Myl1 1690.3 16550.4 18133.5 Top 10 Genes Ckm 282.2 4113.6 8845.7 Acta1 1483.5 17953.5 19931.9 Mybpc2 81.5 164.5 1098.4 Ldb3 235.7 816.1 1938.3

Null module Ankrd1 Kat2b GEO Series "GSE15772" 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=GSE15772 Status: Public on May 20 2009 Title: WT Dorsal Skin Time Course Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19494835 Summary & Design: Summary: Skin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.

Overall design: To gain insights into common and unique transcriptional regulatory programs during epidermal differentiation, we profiled global gene expression in mouse dorsal skin at E14.5, E16.5, and E18.5.

Background corr dist: KL-Divergence = 0.0139, L1-Distance = 0.0232, L2-Distance = 0.0006, Normal std = 0.8175

0.488 Kernel fit Pairwise Correlations Normal fit

Density 0.244

0.000 CEM 1

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

Pre-normalization Quantiles

E14.5 WTE14.5 Dorsal WTE16.5 SkinDorsal WT 1-2E16.5 SkinDorsal (0.248337) WT 1-3E16.5 SkinDorsal (0.218178) WT 6E18.5 (0.0323009) SkinDorsal WT 7E18.5 (0.0248291) SkinDorsal WT 8E18.5 (0.0722287) SkinDorsal WT 5-5 SkinDorsal (0.127229) 6-4 Skin (0.0600451) 1-4 (0.216851)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 211.2 4111.8 6826.7 P ( S | Z, I ) = 1.00 Ryr1 447.7 1326.3 2010.5 Mean Corr = 0.66829 Casq1 92.6 1214.6 3679.1 Tcap 41.0 433.2 691.8 Mypn 113.2 1023.2 1442.3 Cacna1s 5.1 282.0 416.6 Ttn 73.8 243.4 383.8 Ankrd23 52.9 319.5 391.7 Smtnl1 1.3 202.8 656.9 Aldoa 8777.5 14139.3 18240.0 Actc1 4754.1 16732.5 22785.9 Myl3 215.5 300.7 841.8 Ankrd2 21.5 65.6 125.4 Tnnt3 742.4 6997.1 13892.0 Tnni2 531.2 9921.0 18809.1 Tnnc2 947.9 14613.9 22057.0 Myot 100.3 1311.0 3044.1 Mylpf 4773.8 13076.6 23058.8 CEM 1 + Myl1 1848.0 16665.4 27665.5 Top 10 Genes Ckm 53.0 9807.0 17684.6 Acta1 1135.6 20155.8 32222.6 Mybpc2 21.9 93.0 1166.8 Ldb3 110.1 1600.0 2975.2

Null module Ankrd1 Kat2b 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 (0.0120147)C2C12-pMirn0_day (0.0175057)C2C12-pMirn0_day (0.0128066) 3_untreated_rep1C2C12-pMirn0_day 3_untreated_rep2C2C12-pMirn0_day 3_untreated_rep3 C2C12-pMirn0_day(0.0674205) 6_untreated_rep1 C2C12-pMirn0_day(0.0599178) 6_untreated_rep2 C2C12-pMirn0_day(0.0430396) 6_untreated_rep3 C2C12-pMirn0_day(0.0729566) 3_BMP2 C2C12-pMirn0_day(0.0651629) 3_BMP2 treated_rep1 C2C12-pMirn0_day(0.0706313) 3_BMP2 treated_rep2C2C12-pMirn0_day (0.0146186)6_BMP2 treated_rep3C2C12-pMirn378_d0_rep1 (0.0243713)6_BMP2 treated_rep1C2C12-pMirn378_d0_rep2 (0.0223434)6_BMP2 treated_rep2C2C12-pMirn378_d0_rep3 (0.0221618) treated_rep3C2C12-pMirn378_day (0.0125979)(0.0203783)C2C12-pMirn378_day (0.0136121)(0.0213789)C2C12-pMirn378_day (0.013858) 3_untreated_rep1C2C12-pMirn378_day 3_untreated_rep2C2C12-pMirn378_day 3_untreated_rep3C2C12-pMirn378_day (0.0503526) 6_untreated_rep1C2C12-pMirn378_day (0.0504157) 6_untreated_rep2C2C12-pMirn378_day (0.0402343) 6_untreated_rep3C2C12-pMirn378_day (0.051092) 3_BMP2C2C12-pMirn378_day (0.0338812) 3_BMP2C2C12-pMirn378_day treated_rep1 (0.0463189) 3_BMP2C2C12-pMirn378_day treated_rep2 (0.0208427)6_BMP2 treated_rep3 (0.0210492)6_BMP2 treated_rep1 (0.0198441)6_BMP2 treated_rep2 (0.0228175)[ treated_rep3 min (0.0259167) ] (0.0304589)[ medium ] [ max ] CEM 1 Atp2a1 82.4 338.5 6679.7 P ( S | Z, I ) = 1.00 Ryr1 35.6 466.6 5650.9 Mean Corr = 0.66561 Casq1 76.7 672.0 9598.5 Tcap 92.5 296.6 2566.2 Mypn 23.8 73.8 607.9 Cacna1s 10.7 179.9 1908.3 Ttn 30.8 129.1 654.4 Ankrd23 53.6 159.9 2375.4 Smtnl1 2.4 12.0 61.7 Aldoa 10621.7 13524.5 18457.1 Actc1 671.8 4505.6 28041.9 Myl3 23.5 76.6 137.2 Ankrd2 125.5 300.0 7130.8 Tnnt3 570.9 1610.3 24581.9 Tnni2 368.8 1424.5 25840.5 Tnnc2 683.8 3009.6 23267.4 Myot 2.4 127.8 1053.3 Mylpf 4141.3 12041.8 32112.4 CEM 1 + Myl1 9050.0 13936.7 27782.9 Top 10 Genes Ckm 80.1 454.7 10875.6 Acta1 4022.9 12443.5 26374.5 Mybpc2 2.1 27.1 880.9 Ldb3 165.6 321.5 2222.5

Null module Ankrd1 Kat2b GEO Series "GSE7863" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7863 Status: Public on Mar 01 2009 Title: Gene expression profiling of Galgt2 overexpression in mdx skeletal muscle Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Transgenic overexpression of Galgt2 in the skeletal muscles of mdx mice inhibits the development of disease pathology associated with muscular dystrophy. This is the case both in transgenic mice, where Galgt2 overexpression occurs from embryonic timepoints onward and in mdx mice where Galgt2 is overexpressed in the early postnatal period using Adeno-associated virus (AAV). Here, we use gene expression profiling to compare transcriptional changes resulting from embryonic and postnatal Galgt2 overexpression in mdx skeletal muscle. A surprising number of changes were in genes known to ameliorate muscular dystrophy when overexpressed (agrin, integrin alpha 7, ADAM12, Bcl2) or to cause muscular dystrophy when mutated (collagen VI (alpha1,alpha2), plectin 1, dystroglycan, selenoprotein N1, integrin alpha7, biglycan, dysferlin). Several genes involved in calcium homeostasis were also changed. In Galgt2 transgenic mice, where embryonic overexpression of Galgt2 in skeletal muscles alters neuromuscular development and muscle growth, the number of gene expression changes was vastly greater, however, 14% of genes altered in postnatal AAV-Galgt2 infected mdx muscles were also changed with embryonic overexpression. These experiments suggest that postnatal overexpression of Galgt2 inhibits muscular dystrophy in mdx mice via induction of a group of genes that, in aggregate, can govern membrane stability, membrane repair, calcium homeostasis, and apoptosis.

Keywords: disease state analysis, gene therapy, comparative gene expression, muscular dystrophy, glycosylation, collagens, integrins, dysferlin, dystroglycan

Overall design: Microarrays were done in three groups at a time. 1) Transgenic Overexpression of Galgt2 - comprised to Wild Type (WT), Galgt2 Transgenic (CT), Dystrophin-Deficient (mdx), and Galgt2 Transgenic and Dystrophin-Deficient (CTmdx) each in duplicate 2) AAV-Mediated Galgt2 Gene Delivery in to the mdx gastrocnemius muscle in the postnatal period - comprised of AAVGalgt2 and PBS each in duplicate, and 3) Myoblasts and myotubes - comptised of one sample each of C1C12 myoblasts and myotubes, C2C12 myoblasts and myotubes stably transfected with Galgt2

Background corr dist: KL-Divergence = 0.0693, L1-Distance = 0.0383, L2-Distance = 0.0029, Normal std = 0.5016

0.795 Kernel fit Pairwise Correlations Normal fit

Density 0.398

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

GastrocnemiusGastrocnemiusGastrocnemius MuscleGastrocnemius MuscleWT rep1Gastrocnemius MuscleWT (0.045756) rep2Gastrocnemius Musclemdx (0.0623142) rep1Gastrocnemius Musclemdx (0.035692) rep2Gastrocnemius MuscleGalgt2 (0.0669048)Gastrocnemius TransgenicMuscleGalgt2Gastrocnemius TransgenicMuscleGalgt2 rep1Gastrocnemius TransgenicMuscleGalgt2 (0.022466) rep2Gastrocnemius TransgenicMusclemdx (0.0694776) mdx AAV-Galgt2-TreatedMyoblast Musclemdx rep1 mdx AAV-Galgt2-Treated Myoblast(0.028653) Musclemdx Cellrep2 PBS-TreatedLine Myoblast(0.0336838) mdx Cell rep1 PBS-TreatedLineMyoblast (0.0937507)(0.0410867)Cell Differentiatedrep2rep1 Line (0.0522968)(0.020233)Cell Stablyrep2 Line (0.0260579) rep1 TransfectedStably (0.157088) Transfected[ with min Galgt2 with ] rep1Galgt2 (0.146629) Differentiated[ medium rep1 (0.0979113) ] [ max ] CEM 1 Atp2a1 2206.3 18032.3 23821.7 P ( S | Z, I ) = 1.00 Ryr1 3408.4 11441.0 16121.5 Mean Corr = 0.66453 Casq1 99.2 8688.8 11671.3 Tcap 61.7 10110.0 14963.4 Mypn 40.5 4308.1 6930.1 Cacna1s 121.7 1698.0 3386.9 Ttn 372.0 2656.6 4987.3 Ankrd23 122.1 4877.7 9014.8 Smtnl1 28.5 1032.8 2061.5 Aldoa 6934.1 18205.7 22401.7 Actc1 2091.9 9944.1 15338.2 Myl3 62.8 4581.4 8520.8 Ankrd2 461.9 2047.8 3330.1 Tnnt3 3715.6 17125.7 20413.6 Tnni2 2048.6 22266.8 28160.0 Tnnc2 2138.6 21599.5 28547.8 Myot 29.5 10920.6 13206.2 Mylpf 8469.5 18867.9 24524.3 CEM 1 + Myl1 6947.5 18405.5 24754.2 Top 10 Genes Ckm 88.1 7392.5 13800.6 Acta1 3901.3 18956.9 21869.0 Mybpc2 62.0 14870.0 19615.0 Ldb3 165.8 6477.2 10413.9

Null module Ankrd1 Kat2b GEO Series "GSE16377" 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=GSE16377 Status: Public on Jun 01 2010 Title: wild type mouse lung control vs. high fat diet Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To study the effects of a high fat diet on the mouse lung transcrptional profile.

Overall design: 6 samples were analyzed. 3 wild type mice on a control diet (lung samples) vs. 3 wild type mice on a high fat diet (lung samples).

Background corr dist: KL-Divergence = 0.0411, L1-Distance = 0.0234, L2-Distance = 0.0007, Normal std = 0.6141

0.658 Kernel fit Pairwise Correlations Normal fit

Density 0.329

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_lung_1317control_lung_1321control_lung_1391 (0.384191)fat_diet_lung_1711 (0.15409)fat_diet_lung_1713 (0.0639802)fat_diet_lung_1715 (0.2441) (0.0741732) (0.0794647)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 66.7 288.0 2487.5 P ( S | Z, I ) = 1.00 Ryr1 82.7 95.4 764.2 Mean Corr = 0.66312 Casq1 99.5 168.2 978.4 Tcap 1350.1 3089.8 8294.8 Mypn 44.7 120.2 419.8 Cacna1s 8.5 48.6 132.9 Ttn 6.5 77.9 131.7 Ankrd23 7.2 21.3 174.9 Smtnl1 2.1 81.0 404.6 Aldoa 6564.7 10188.6 14949.2 Actc1 5448.4 12383.4 27635.6 Myl3 145.2 676.0 4951.4 Ankrd2 12.2 34.6 46.8 Tnnt3 49.5 288.9 6845.9 Tnni2 19.9 338.9 8165.1 Tnnc2 3.4 512.2 14315.2 Myot 4.4 106.4 1527.4 Mylpf 75.9 231.7 6171.9 CEM 1 + Myl1 64.5 1065.5 8822.6 Top 10 Genes Ckm 209.8 970.2 7486.7 Acta1 68.3 1295.8 20301.1 Mybpc2 15.6 78.6 1444.7 Ldb3 122.2 477.5 1868.6

Null module Ankrd1 Kat2b GEO Series "GSE30688" 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=GSE30688 Status: Public on Jul 15 2011 Title: Gene expression profiles of mouse sentinel lymph nodes (SLNs) in xenotransplanted and non tumor bearing CB17 SCID. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Cutaneous melanoma first metastasizes into sentinel lymph nodes that control the lymphatic drain from the area of the primary tumor. This observation is used clinically for melanoma patients with primary melanomas thicker than 1mm (tumor stage ¥T2a), for these patients sentinel lymph node biopsy has become an important and routinely performed diagnostic procedure. The importance of sentinel node analysis is reflected by a significant better prognosis of melanoma patients with tumor free sentinel nodes compared to patients with metastatic sentinel nodes. Although intensively studied, not much is known about mechanisms responsible for the development of melanoma metastasis.To analyze gene expression in mouse SLNs of M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. After categorized SLNs were subjected to microarray analysis.

Overall design: To analyze gene expression in mouse SLNs of human M24met tumor bearing animals as compared to tumor free control animals, SLNs were taken at different time points and analyzed for the presence of human M24met to classify SLNs into control, negative, macro metastatic SLN. Briefly, explanted SLNs were stored in RNA later (Ambion, Austin, TX) and DNA as well as RNA was extracted using AllPrep DNA/RNA Mini Kit and RNeasy Micro Kit (Qiagen, Valencia, CA) according to manufacturers instructions. To detect human cells in mouse SLNs we used a polymerase chain reaction method for the detection of a human-specific 850-bp fragment of the alpha-satellite DNA on human chromosome 17. For analysis of gene expression RNA from control SLN from tumor free animals (control), RNA from tumor negative SLN (negative), and RNA from macro metastatic SLN (positive) from tumor bearing animals was used to analyze gene expression on Mouse Genome 430A 2.0 Arrays (Affymetrix, Santa Clara, CA)

Background corr dist: KL-Divergence = 0.0518, L1-Distance = 0.0285, L2-Distance = 0.0014, Normal std = 0.5507

0.724 Kernel fit Pairwise Correlations Normal fit

Density 0.362

0.000 CEM 1

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

Pre-normalization Quantiles

Ca (0.0782834)Cb (0.0637652)Cc (0.0545137)Na (0.142748)Nb (0.0708222)Nc (0.074114)Pa (0.0465777)Pb (0.433362)Pd (0.0358144) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 129.2 599.7 12755.9 P ( S | Z, I ) = 1.00 Ryr1 131.1 230.6 1127.7 Mean Corr = 0.66302 Casq1 49.0 123.5 2578.7 Tcap 44.5 88.2 1868.1 Mypn 40.4 63.6 309.3 Cacna1s 95.9 158.1 331.3 Ttn 33.9 49.3 85.1 Ankrd23 44.9 71.1 237.2 Smtnl1 28.7 36.0 68.1 Aldoa 8026.8 16111.1 28288.2 Actc1 54.5 97.6 480.8 Myl3 66.4 79.1 123.1 Ankrd2 61.7 102.5 155.4 Tnnt3 40.7 194.3 8338.8 Tnni2 146.2 281.0 9296.5 Tnnc2 39.3 586.4 21771.9 Myot 28.1 39.1 883.4 Mylpf 70.4 336.5 7327.0 CEM 1 + Myl1 125.1 1493.6 11822.4 Top 10 Genes Ckm 82.4 563.0 17473.5 Acta1 115.2 1648.5 37904.4 Mybpc2 37.8 114.4 2774.4 Ldb3 31.7 52.1 521.5

Null module Ankrd1 Kat2b GEO Series "GSE17739" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17739 Status: Public on Oct 22 2009 Title: Circadian gene profiling in the distal nephron and collecting ducts Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19805330 Summary & Design: Summary: Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.

Keywords: time course

Overall design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.

Background corr dist: KL-Divergence = 0.0374, L1-Distance = 0.0298, L2-Distance = 0.0014, Normal std = 0.6138

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

DCT/CNT_ZT0_pool1DCT/CNT_ZT0_pool2DCT/CNT_ZT4_pool1 (0.0262069)DCT/CNT_ZT4_pool2 (0.028762)DCT/CNT_ZT8_pool1 (0.029601)DCT/CNT_ZT8_pool2 (0.0244184)DCT/CNT_ZT12_pool1 (0.0796086)DCT/CNT_ZT12_pool2 (0.0273957)DCT/CNT_ZT16_pool1 DCT/CNT_ZT16_pool2(0.0813452) DCT/CNT_ZT20_pool1(0.0357384) DCT/CNT_ZT20_pool2(0.066819) CCD_ZT0_pool1(0.0667815) CCD_ZT0_pool2(0.107192) CCD_ZT4_pool1(0.0302377) (0.0384517)CCD_ZT4_pool2 (0.0231666)CCD_ZT8_pool1 (0.0481452)CCD_ZT8_pool2 (0.0451539)CCD_ZT12_pool1 (0.0204881)CCD_ZT12_pool2 (0.0256428)CCD_ZT16_pool1 (0.0326696)CCD_ZT16_pool2 (0.0312353)CCD_ZT20_pool1 (0.0299812)CCD_ZT20_pool2 (0.0346262) (0.0267954) (0.0395377) [ min ] [ medium ] [ max ] CEM 1 Atp2a1 102.1 139.1 217.2 P ( S | Z, I ) = 1.00 Ryr1 25.9 70.1 121.4 Mean Corr = 0.66252 Casq1 22.4 38.6 88.4 Tcap 93.3 233.6 402.3 Mypn 11.3 20.1 59.5 Cacna1s 15.2 23.7 47.5 Ttn 20.0 30.6 60.5 Ankrd23 115.1 142.1 178.9 Smtnl1 42.2 72.3 101.3 Aldoa 15170.9 18746.8 21289.6 Actc1 8.3 12.3 20.8 Myl3 113.1 179.2 286.0 Ankrd2 71.2 111.1 157.1 Tnnt3 35.5 69.9 108.1 Tnni2 126.4 207.3 264.0 Tnnc2 96.5 173.5 259.2 Myot 9.8 15.1 25.1 Mylpf 125.9 200.1 257.2 CEM 1 + Myl1 23.0 49.2 184.0 Top 10 Genes Ckm 54.4 96.0 127.9 Acta1 29.9 44.1 59.3 Mybpc2 29.0 60.2 96.5 Ldb3 36.7 77.5 119.0

Null module Ankrd1 Kat2b GEO Series "GSE5657" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5657 Status: Public on Feb 06 2007 Title: Effect of X-linked hypophosphatemia (the Hyp mutation) on gene expression in the mid-shaft of the mouse femur Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The pathophysiology of the osteomalacia in X-linked hypophosphatemia is uncertain. In this project, genomic DNA microarrays were used to identify novel genes with abnormal mRNA expression levels in mice with the dominant Hyp mutation of the Phex gene. Femoral shafts from five-week-old C57BL/6J mice, male and female, normal and Hyp (hemizygous male and heterozygous female), were flushed with saline to remove the marrow. RNA was extracted from each bone, pooled between two mice for each array, processed to cRNA, and hybridized to Affymetrix Mouse 430 2.0 GeneChip microarrays with probe sets for 45,101 genes. Twenty microarrays (40 mice) were done with 5 arrays for each treatment group (normal male, Hyp male, normal female and Hyp female). For each gene, factorial analysis of variance was performed for the main effects of genotype (normal vs. Hyp), sex (male vs. female), and genotype-by-sex interaction. The mRNA levels for 54 % of the genes on each array were scored as present. At P < 0.01, 2,635 genes were significant for genotype, 1,488 for sex, and 509 for genotype-by-sex interaction. There were two probes sets for the Phex gene. Probe 1450445, at the 3 end of the coding sequence, was low in normal samples (246 ´– 37 (10), mean ´– SEM (n)) and absent in Hyp samples. Probe 1421979, at the far 3 end of the untranslated region of the cDNA, 3,000 base pairs from the coding sequence, was high in normal mice (3,915 Â± 315 (10); 8x brighter than the average gene), undetectable in Hyp males, and 725 Â± 93 (5) in Hyp females. Both probe sets were scored as absent in kidney tissue. In Hyp bone, male and female, there was significant down-regulation of markers of osteoblasts and bone matrix synthesis with significant up-regulation of markers of blood vessel formation and cytoskeleton. No prominent skeletal gene was up-regulated in Hyp to attempt to compensate for the low skeletal mineralization. The genes with significant genotype-by-sex interaction did not show a marked fold difference between male and female Hyp mice. In conclusion, male and female Hyp mice showed similar depression of mRNA levels of genes related to bone synthesis in the femoral shaft. There was a high signal level from probes for a sequence in the 3 untranslated region of the Phex gene of normal, but not Hyp, mice, suggesting the need for further study of the molecular organization of this gene.

Keywords: 2x2 factorial design with complete blocks

Overall design: Equal amounts of RNA from two mice, matched for genotype and sex were pooled to create each sample for microarray analysis. Four treatment groups were done: (1) Normal male mice, (2) Hyp male mice, (3) normal female mice, and (4) Hyp female mice. Five replicates were done with each replicate containing one sample from each of the four treatment groups for a total of 20 independent samples (40 mice total). Each replicate was matched for littermates and parallel processing.

Background corr dist: KL-Divergence = 0.2840, L1-Distance = 0.0582, L2-Distance = 0.0087, Normal std = 0.2875

1.387 Kernel fit Pairwise Correlations Normal fit

Density 0.694

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

Series 1:Series Normal 1:Series HypMale 1:maleSeries (0.103642) Normal (0.0497892) 1:Series Hypfemale 2:femaleSeries Normal(0.127599) (0.0270877)2:Series Hypmale 2:maleSeries (0.0401222) Normal (0.0205344) 2:Series Hypfemale 3:femaleSeries Normal(0.0333775) (0.163432)3:Series Hypmale 3:maleSeries (0.0436196) Normal (0.0468467) 3:Series Hypfemale 4:femaleSeries Normal(0.0269403) (0.0177933)4:Series Hypmale 4:maleSeries (0.0262154) Normal (0.0494193) 4:Series Hypfemale 5:femaleSeries Normal(0.0324911) (0.01129)5:Series Hypmale 5:maleSeries (0.0857744) Normal (0.0321657) 5: Hypfemale female (0.0277591) (0.0341015)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 21970.0 32227.1 56159.0 P ( S | Z, I ) = 1.00 Ryr1 3619.0 10768.2 16551.1 Mean Corr = 0.66108 Casq1 10347.4 15730.8 31152.9 Tcap 4028.3 10328.4 22994.8 Mypn 950.1 2070.7 4332.1 Cacna1s 758.3 1986.9 3168.4 Ttn 336.0 724.2 1257.3 Ankrd23 2820.8 6856.6 10835.3 Smtnl1 307.0 937.6 2698.3 Aldoa 27427.9 37482.4 64913.1 Actc1 3157.7 19029.4 35296.7 Myl3 624.2 4126.9 10656.8 Ankrd2 346.0 1451.2 4419.3 Tnnt3 26752.8 42139.4 62248.2 Tnni2 25227.5 38252.0 61964.9 Tnnc2 27879.0 38332.7 58864.5 Myot 5720.5 14614.4 25380.6 Mylpf 28688.1 35982.1 56905.3 CEM 1 + Myl1 33179.1 44371.7 66644.3 Top 10 Genes Ckm 27451.8 38509.7 58315.9 Acta1 36821.1 50310.0 75138.1 Mybpc2 8699.7 13953.1 28246.0 Ldb3 4364.8 8516.6 18109.0

Null module Ankrd1 Kat2b GEO Series "GSE17825" 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=GSE17825 Status: Public on Sep 01 2009 Title: Murine fracture healing Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18752025 Summary & Design: Summary: Time-point expression analysis of fractures calluses at 1, 3, and 5 days post-fracture in young and old BALB/c mice.

Overall design: Femur fractures were generated on female c57BI6 mice in triplicate: 8 month old retired breeders (old mice) and 6 week old mice (young mice) were used. 1, 3, and 5 days post-fracture, fracture calluses were dissected and total RNA isolated. Expression profiling was performed using Affymetrix's Mouse Genome 430 2.0 array.

Background corr dist: KL-Divergence = 0.0962, L1-Distance = 0.0386, L2-Distance = 0.0030, Normal std = 0.4412

0.904 Kernel fit Pairwise Correlations Normal fit

Density 0.452

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

old murineold murine1 dayold post-fracture murine1 dayyoung post-fracture 1 day murineyoung (replicate post-fracture murine1young (replicateday 1) post-fracture(0.146545) murine1old (replicateday 2)murine post-fracture(0.00823614) 1old day 3) murine3(replicate post-fracturedays(0.0854812)old post-fracture murine3(replicate days 1)young (0.0605466) post-fracture 3(replicate days 2)murineyoung (0.0771825)(replicate post-fracture 3)murine3young days (0.081462)(replicate 1) post-fracturemurine3(0.022817)old days (replicate murine 2) post-fracture3(0.0257574)old days murine5 3) (replicatedays post-fracture(0.0214783)old post-fracturemurine5 (replicatedays young1) (0.0934739) post-fracture5 (replicatedays murine young2) (replicate (0.0986276) post-fracture murine5 young3) days (replicate (0.0260944) 1) post-fracturemurine5(0.0343931) days (replicate 2) post-fracture5(0.0131396) days 3) (replicate post-fracture(0.035119) (replicate [1) min(0.0383248) (replicate 2) (0.0605307) ] 3) (0.0707906)[ medium ] [ max ] CEM 1 Atp2a1 761.2 31993.1 93386.6 P ( S | Z, I ) = 1.00 Ryr1 303.0 8999.0 26204.6 Mean Corr = 0.66039 Casq1 279.8 6881.4 13475.3 Tcap 351.6 9995.7 18719.3 Mypn 133.2 2414.6 8266.4 Cacna1s 9.8 1784.2 4235.9 Ttn 56.9 570.1 1634.4 Ankrd23 653.4 9986.9 18663.0 Smtnl1 21.3 520.9 1788.2 Aldoa 10679.4 43212.9 100694.6 Actc1 252.7 4705.2 17829.2 Myl3 158.6 1950.7 22037.0 Ankrd2 114.6 1659.2 26938.8 Tnnt3 1125.4 42252.5 101705.1 Tnni2 1523.8 45112.6 103715.4 Tnnc2 1613.8 42365.2 102726.4 Myot 310.5 8468.8 25173.0 Mylpf 3597.3 44546.8 80932.2 CEM 1 + Myl1 3036.4 43898.3 93229.4 Top 10 Genes Ckm 1529.8 44687.3 101291.6 Acta1 2929.0 53562.0 142840.8 Mybpc2 298.5 19309.9 41268.6 Ldb3 61.4 5505.9 15733.3

Null module Ankrd1 Kat2b GEO Series "GSE9330" 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=GSE9330 Status: Public on Dec 15 2007 Title: Expression data from wild type and Ctip2-/- (Bcl11b) mutant mouse striatum at P0 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18199763 Summary & Design: Summary: Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntingtons disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.

Keywords: mutant analysis

Overall design: Matched regions of striatum from wild type and Ctip2-/- mice were obtained via 500 ´m diameter punch biopsies performed in the center of the developing striatum in acutely sectioned 300 ´m coronal slices of the brain at postnatal day 0 (P0). Sections were matched rostro-caudally between wild type and null mutant tissue, and fiduciary landmarks were used to assure reproducible microdissection of comparable regions. RNA was extracted using the StrataPrep Total RNA Mini Kit (Stratagene, La Jolla, CA), and RNA quality was assayed using a bioanalyzer (Agilent Technologies, Paola Alto, CA). To ensure reproducibility and biological significance, microarrays were performed with RNA samples from three independent wild type, one heterozygote, and four Ctip2-/- mice (biological replicates). Microarray data were normalized using the RMA function within Bioconductor (Irizarry et al., 2003). Statistical significance of gene expression differences between wild type and knockout was determined using Statistical Analysis of Micrarrays (SAM) (Tusher et al., 2001). Using a SAM d-score cutoff of > 2 or < -2, we selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance.

Background corr dist: KL-Divergence = 0.0229, L1-Distance = 0.0600, L2-Distance = 0.0051, Normal std = 0.7875

0.507 Kernel fit Pairwise Correlations Normal fit

Density 0.253

0.000 CEM 1

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

Pre-normalization Quantiles

striatum_wildtype_1striatum_wildtype_2striatum_wildtype_3 (0.0374378)striatum_het_1 (0.290212)striatum_ctip2_KO_1 (0.166328)striatum_ctip2_KO_2 (0.1469)striatum_ctip2_KO_3 (0.0439371)striatum_ctip2_KO_4 (0.0748087) (0.165943) (0.0744334)[ min ] [ medium ] [ max ] CEM 1 Atp2a1 137.0 180.6 235.6 P ( S | Z, I ) = 1.00 Ryr1 59.5 80.4 104.9 Mean Corr = 0.67126 Casq1 230.5 313.0 393.1 Tcap 113.4 132.2 180.4 Mypn 112.8 143.7 274.6 Cacna1s 57.3 76.8 81.4 Ttn 33.4 44.3 55.8 Ankrd23 145.6 177.1 227.1 Smtnl1 97.9 149.5 223.8 Aldoa 2765.4 4051.2 5181.4 Actc1 181.7 241.0 273.8 Myl3 300.7 393.8 571.0 Ankrd2 334.3 436.3 914.5 Tnnt3 67.1 82.7 121.9 Tnni2 78.6 115.8 154.4 Tnnc2 63.7 69.2 98.3 Myot 37.7 55.8 72.7 Mylpf 114.3 174.6 212.0 CEM 1 + Myl1 112.0 147.7 221.2 Top 10 Genes Ckm 203.9 266.6 374.3 Acta1 202.6 226.6 248.5 Mybpc2 52.5 69.2 110.9 Ldb3 132.2 168.7 198.2

Null module Ankrd1 Kat2b