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

Dataset: Num of genes in input gene set: 47 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. B230216G23Rik 1500015O10Rik 0610007P14Rik Tmem168 Crispld2 Num ofGenesinQueryGeneset:47.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Bloc1s5 Bloc1s3 Bloc1s6 Galnt15 Rab11a Plekhf2 Col6a3 Col6a1 Col6a2 Exoc3l Ovgp1 Aph1b Rab3d Ap1g2 Aimp1 Cdk16 Ap3s1 Pcsk2 Pcsk1 Ap1ar Nrsn2 Nrsn1 Nptx1 Syt13 Myrip Gnas Cpa3 Yipf3 Yipf1 Yipf2 Sspn Cav2 Prg2 Cnst Stx2 Pigr Bgn Astl Shh Hck Vgf Nts

Col6a2 Col6a1 Col6a3 Bgn Sspn Crispld2 Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip 0.0 Singletons CEM 1(611datasets) Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Symbol Num ofCEMGenes:6.Predicted183.SelectedDatasets:611.Strength:11.5 CEM 1,Geneset"[G]transportvesicle",Page1 Tmem119 Serpinh1 Adamts2 Serpinf1 Crispld2 Col12a1 Efemp2 Leprel2 Ccdc80 Fkbp10 Col3a1 Col5a1 Col1a1 Col5a2 Col1a2 Col6a3 Col6a1 Col6a2 Col4a1 Col4a2 Pcolce Pdgfrb Lama2 Lama4 Olfml3 Cdh11 Aebp1 Cd248 Igfbp7 Fkbp7 Thbs2 Mxra8 Mmp2 Sparc Postn Bicc1 Fbln5 Loxl2 Rcn3 Sspn Fstl1 Nid1 Lhfp Ppic Lum Mgp Bgn Lox Dpt Islr 0.0 1.0

GSE16925 [15] GSE35785 [10]

GSE13106 [10] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE18907 [12] GSE44339 [14] GSE6383 [6] GSE14395 [24] GSE39391 [21] GSE51608 [6] GSE14354 [6] GSE40368 [10] GSE56542 [8] GSE19979 [6] GSE4193 [8] GSE53299 [6] GSE5038 [9] GSE12956 [10] GSE8044 [6] GSE12618 [6] GSE27848 [16] GSE41759 [14] GSE54349 [6] GSE40156 [42] GSE44101 [6] GSE41342 [26] GSE42601 [6] GSE26299 [108] GSE5671 [18] GSE7694 [12] GSE45820 [6] GSE23845 [15] GSE15267 [8] GSE7810 [9] GSE9013 [12] GSE13302 [30] GSE10556 [6] GSE13874 [14] GSE34618 [7] GSE11898 [9] GSE18281 [33] GSE11759 [6] GSE37191 [12] GSE48790 [8] GSE54207 [9] GSE25029 [56] GSE28277 [10] GSE18534 [15] GSE27987 [31] GSE34552 [10] GSE6210 [12] GSE16691 [12] GSE42008 [6] GSE6589 [11] GSE5037 [18] GSE35091 [11] GSE47772 [24] GSE36229 [14] GSE35396 [24] GSE9400 [8] GSE8025 [21] GSE31244 [6] GSE10813 [12] GSE35961 [12] GSE49346 [6] GSE42753 [6] GSE24625 [12] GSE26290 [12] GSE47777 [8] GSE28664 [17] GSE13044 [59] GSE13526 [6] GSE32334 [19] GSE53403 [16] GSE13408 [14] GSE39984 [18] GSE6881 [10] GSE18660 [10] GSE23408 [39] GSE27630 [8] GSE29485 [12] GSE27932 [14] GSE7069 [8] GSE32277 [33] GSE24793 [8] GSE20577 [12] GSE52550 [12] GSE22925 [14] GSE40856 [8] GSE27261 [8] GSE7342 [12] GSE27546 [51] GSE15580 [14] GSE50824 [19] GSE29813 [18] GSE15794 [6] GSE15772 [8] GSE28389 [20] GSE29766 [40] GSE17462 [8] GSE59672 [12] GSE20177 [14] GSE7020 [8] GSE13563 [6] GSE9098 [12] GSE52101 [17] GSE24295 [7] GSE8024 [8] GSE32966 [24] GSE11148 [6] GSE33134 [31] GSE30855 [6] GSE18135 [18] GSE27568 [16] GSE58307 [20] GSE11443 [6] GSE38257 [14] GSE32095 [24] GSE32937 [8] GSE29975 [6] GSE5011 [10] GSE22371 [6] GSE34091 [8] GSE31431 [34] GSE27713 [7] GSE23598 [8] GSE30852 [6] GSE43779 [6] GSE18586 [9] GSE53951 [10] GSE5245 [16] GSE10965 [8] GSE18587 [9] GSE7196 [6] GSE33471 [12] GSE12498 [12] GSE44175 [18] GSE8788 [6] GSE5333 [16] GSE4695 [6] GSE15401 [18] GSE51686 [9] GSE10113 [12] GSE16496 [102] GSE9123 [8] GSE33726 [48] GSE38224 [12] GSE45968 [6] GSE14481 [12] GSE9044 [6] GSE55162 [8] GSE24276 [6] GSE22989 [10] GSE9711 [6] GSE19793 [32] CEM+ CEM GSE15155 [12] GSE51213 [16] GSE51483 [45] GSE21576 [10] GSE52474 [154] GSE35322 [20] 0.0 GSE14088 [9] GSE22841 [12]

GSE4230 [8] Scale ofaveragePearsoncorrelations GSE19194 [14] GSE18742 [13] GSE6540 [12] GSE31106 [18] GSE42049 [8] GSE51628 [15] 0.2 GSE6867 [6] GSE36415 [14] GSE51432 [15] GSE17373 [24] GSE50439 [15] GSE30561 [6] GSE51108 [6] GSE31013 [12] GSE27302 [16] 0.4 GSE9735 [9] GSE22251 [9] GSE56777 [8] GSE59437 [30] GSE17797 [19] GSE34279 [30] GSE9892 [12] GSE30863 [20] GSE20523 [17] 0.6 GSE31598 [12] GSE53986 [16] GSE22307 [23] GSE46211 [18] GSE13963 [15] GSE13148 [10] GSE16790 [18] GSE15729 [15] GSE17817 [6] 0.8 GSE18395 [8] GSE33860 [28] GSE33308 [10] GSE32598 [11] Score 59.90 59.93 60.05 60.47 60.73 62.20 63.21 63.80 66.16 67.96 69.43 69.75 71.99 73.39 74.07 76.41 77.08 77.93 78.02 78.03 79.22 79.75 81.29 82.82 87.62 88.06 89.67 90.12 91.69 99.88 100.50 101.60 102.94 104.83 110.87 116.01 118.66 123.72 125.23 147.40 158.25 166.57 168.73 187.35 1.0 Notes Symbol Num ofCEMGenes:6.Predicted183.SelectedDatasets:611.Strength:11.5 CEM 1,Geneset"[G]transportvesicle",Page2 Fam114a1 Adamts12 Tmem45a Prkcdbp Col15a1 Col16a1 Olfml2b Emilin1 Tgfb1i1 Fkbp14 Gpr153 Gpr124 Mmp23 B3gnt9 Scara3 Smoc2 Pmp22 Kdelr3 Lrrc17 Scarf2 Copz2 Svep1 Fkbp9 Pdgfrl Mfap4 Mfap5 Matn2 Ednra Srpx2 Ltbp3 Tgfb3 Tagln Loxl3 Crtap Htra3 Gpx7 Aspn Cd34 Pxdn Cav1 Reck Srpx Myl9 Rhoj Ctsk Slit3 Ogn Gsn Tnc Fn1 0.0 1.0

GSE16925 [15] GSE35785 [10]

GSE13106 [10] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE18907 [12] GSE44339 [14] GSE6383 [6] GSE14395 [24] GSE39391 [21] GSE51608 [6] GSE14354 [6] GSE40368 [10] GSE56542 [8] GSE19979 [6] GSE4193 [8] GSE53299 [6] GSE5038 [9] GSE12956 [10] GSE8044 [6] GSE12618 [6] GSE27848 [16] GSE41759 [14] GSE54349 [6] GSE40156 [42] GSE44101 [6] GSE41342 [26] GSE42601 [6] GSE26299 [108] GSE5671 [18] GSE7694 [12] GSE45820 [6] GSE23845 [15] GSE15267 [8] GSE7810 [9] GSE9013 [12] GSE13302 [30] GSE10556 [6] GSE13874 [14] GSE34618 [7] GSE11898 [9] GSE18281 [33] GSE11759 [6] GSE37191 [12] GSE48790 [8] GSE54207 [9] GSE25029 [56] GSE28277 [10] GSE18534 [15] GSE27987 [31] GSE34552 [10] GSE6210 [12] GSE16691 [12] GSE42008 [6] GSE6589 [11] GSE5037 [18] GSE35091 [11] GSE47772 [24] GSE36229 [14] GSE35396 [24] GSE9400 [8] GSE8025 [21] GSE31244 [6] GSE10813 [12] GSE35961 [12] GSE49346 [6] GSE42753 [6] GSE24625 [12] GSE26290 [12] GSE47777 [8] GSE28664 [17] GSE13044 [59] GSE13526 [6] GSE32334 [19] GSE53403 [16] GSE13408 [14] GSE39984 [18] GSE6881 [10] GSE18660 [10] GSE23408 [39] GSE27630 [8] GSE29485 [12] GSE27932 [14] GSE7069 [8] GSE32277 [33] GSE24793 [8] GSE20577 [12] GSE52550 [12] GSE22925 [14] GSE40856 [8] GSE27261 [8] GSE7342 [12] GSE27546 [51] GSE15580 [14] GSE50824 [19] GSE29813 [18] GSE15794 [6] GSE15772 [8] GSE28389 [20] GSE29766 [40] GSE17462 [8] GSE59672 [12] GSE20177 [14] GSE7020 [8] GSE13563 [6] GSE9098 [12] GSE52101 [17] GSE24295 [7] GSE8024 [8] GSE32966 [24] GSE11148 [6] GSE33134 [31] GSE30855 [6] GSE18135 [18] GSE27568 [16] GSE58307 [20] GSE11443 [6] GSE38257 [14] GSE32095 [24] GSE32937 [8] GSE29975 [6] GSE5011 [10] GSE22371 [6] GSE34091 [8] GSE31431 [34] GSE27713 [7] GSE23598 [8] GSE30852 [6] GSE43779 [6] GSE18586 [9] GSE53951 [10] GSE5245 [16] GSE10965 [8] GSE18587 [9] GSE7196 [6] GSE33471 [12] GSE12498 [12] GSE44175 [18] GSE8788 [6] GSE5333 [16] GSE4695 [6] GSE15401 [18] GSE51686 [9] GSE10113 [12] GSE16496 [102] GSE9123 [8] GSE33726 [48] GSE38224 [12] GSE45968 [6] GSE14481 [12] GSE9044 [6] GSE55162 [8] GSE24276 [6] GSE22989 [10] GSE9711 [6] GSE19793 [32] CEM+ CEM GSE15155 [12] GSE51213 [16] GSE51483 [45] GSE21576 [10] GSE52474 [154] GSE35322 [20] 0.0 GSE14088 [9] GSE22841 [12]

GSE4230 [8] Scale ofaveragePearsoncorrelations GSE19194 [14] GSE18742 [13] GSE6540 [12] GSE31106 [18] GSE42049 [8] GSE51628 [15] 0.2 GSE6867 [6] GSE36415 [14] GSE51432 [15] GSE17373 [24] GSE50439 [15] GSE30561 [6] GSE51108 [6] GSE31013 [12] GSE27302 [16] 0.4 GSE9735 [9] GSE22251 [9] GSE56777 [8] GSE59437 [30] GSE17797 [19] GSE34279 [30] GSE9892 [12] GSE30863 [20] GSE20523 [17] 0.6 GSE31598 [12] GSE53986 [16] GSE22307 [23] GSE46211 [18] GSE13963 [15] GSE13148 [10] GSE16790 [18] GSE15729 [15] GSE17817 [6] 0.8 GSE18395 [8] GSE33860 [28] GSE33308 [10] GSE32598 [11] Score 29.05 29.57 30.00 30.03 30.47 30.73 30.81 30.98 31.52 32.47 32.66 35.86 36.63 36.63 37.04 37.10 38.04 38.71 38.86 39.24 39.40 39.80 41.23 41.90 42.01 43.15 43.80 44.04 44.68 44.78 45.38 45.55 45.82 45.91 46.33 47.35 50.55 50.77 52.13 52.81 52.87 53.46 53.57 53.62 55.73 56.29 56.64 57.19 58.04 58.95 1.0 Notes Symbol Num ofCEMGenes:6.Predicted183.SelectedDatasets:611.Strength:11.5 CEM 1,Geneset"[G]transportvesicle",Page3 Fam198b Serping1 Adamts5 Colec12 Col14a1 C1qtnf2 Creb3l1 Sparcl1 Cyp1b1 Efemp1 Casp12 Fndc3b Myadm Cmtm3 Col5a3 Kdelc2 Lepre1 Lamb1 Lgals1 Lamc1 Cspg4 Abca9 Anxa5 Vstm4 Wwtr1 Igfbp6 Eva1b Wisp1 Mfap2 Actg2 Emp3 Ltbp2 Fmod Itm2a Loxl1 Htra1 Gpx8 Gas1 Ehd2 Ptgis Dkk3 Pkd2 Tns1 Nbl1 Calu Dsel Ctgf Vim Fap Axl 0.0 1.0

GSE16925 [15] GSE35785 [10]

GSE13106 [10] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE18907 [12] GSE44339 [14] GSE6383 [6] GSE14395 [24] GSE39391 [21] GSE51608 [6] GSE14354 [6] GSE40368 [10] GSE56542 [8] GSE19979 [6] GSE4193 [8] GSE53299 [6] GSE5038 [9] GSE12956 [10] GSE8044 [6] GSE12618 [6] GSE27848 [16] GSE41759 [14] GSE54349 [6] GSE40156 [42] GSE44101 [6] GSE41342 [26] GSE42601 [6] GSE26299 [108] GSE5671 [18] GSE7694 [12] GSE45820 [6] GSE23845 [15] GSE15267 [8] GSE7810 [9] GSE9013 [12] GSE13302 [30] GSE10556 [6] GSE13874 [14] GSE34618 [7] GSE11898 [9] GSE18281 [33] GSE11759 [6] GSE37191 [12] GSE48790 [8] GSE54207 [9] GSE25029 [56] GSE28277 [10] GSE18534 [15] GSE27987 [31] GSE34552 [10] GSE6210 [12] GSE16691 [12] GSE42008 [6] GSE6589 [11] GSE5037 [18] GSE35091 [11] GSE47772 [24] GSE36229 [14] GSE35396 [24] GSE9400 [8] GSE8025 [21] GSE31244 [6] GSE10813 [12] GSE35961 [12] GSE49346 [6] GSE42753 [6] GSE24625 [12] GSE26290 [12] GSE47777 [8] GSE28664 [17] GSE13044 [59] GSE13526 [6] GSE32334 [19] GSE53403 [16] GSE13408 [14] GSE39984 [18] GSE6881 [10] GSE18660 [10] GSE23408 [39] GSE27630 [8] GSE29485 [12] GSE27932 [14] GSE7069 [8] GSE32277 [33] GSE24793 [8] GSE20577 [12] GSE52550 [12] GSE22925 [14] GSE40856 [8] GSE27261 [8] GSE7342 [12] GSE27546 [51] GSE15580 [14] GSE50824 [19] GSE29813 [18] GSE15794 [6] GSE15772 [8] GSE28389 [20] GSE29766 [40] GSE17462 [8] GSE59672 [12] GSE20177 [14] GSE7020 [8] GSE13563 [6] GSE9098 [12] GSE52101 [17] GSE24295 [7] GSE8024 [8] GSE32966 [24] GSE11148 [6] GSE33134 [31] GSE30855 [6] GSE18135 [18] GSE27568 [16] GSE58307 [20] GSE11443 [6] GSE38257 [14] GSE32095 [24] GSE32937 [8] GSE29975 [6] GSE5011 [10] GSE22371 [6] GSE34091 [8] GSE31431 [34] GSE27713 [7] GSE23598 [8] GSE30852 [6] GSE43779 [6] GSE18586 [9] GSE53951 [10] GSE5245 [16] GSE10965 [8] GSE18587 [9] GSE7196 [6] GSE33471 [12] GSE12498 [12] GSE44175 [18] GSE8788 [6] GSE5333 [16] GSE4695 [6] GSE15401 [18] GSE51686 [9] GSE10113 [12] GSE16496 [102] GSE9123 [8] GSE33726 [48] GSE38224 [12] GSE45968 [6] GSE14481 [12] GSE9044 [6] GSE55162 [8] GSE24276 [6] GSE22989 [10] GSE9711 [6] GSE19793 [32] CEM+ CEM GSE15155 [12] GSE51213 [16] GSE51483 [45] GSE21576 [10] GSE52474 [154] GSE35322 [20] 0.0 GSE14088 [9] GSE22841 [12]

GSE4230 [8] Scale ofaveragePearsoncorrelations GSE19194 [14] GSE18742 [13] GSE6540 [12] GSE31106 [18] GSE42049 [8] GSE51628 [15] 0.2 GSE6867 [6] GSE36415 [14] GSE51432 [15] GSE17373 [24] GSE50439 [15] GSE30561 [6] GSE51108 [6] GSE31013 [12] GSE27302 [16] 0.4 GSE9735 [9] GSE22251 [9] GSE56777 [8] GSE59437 [30] GSE17797 [19] GSE34279 [30] GSE9892 [12] GSE30863 [20] GSE20523 [17] 0.6 GSE31598 [12] GSE53986 [16] GSE22307 [23] GSE46211 [18] GSE13963 [15] GSE13148 [10] GSE16790 [18] GSE15729 [15] GSE17817 [6] 0.8 GSE18395 [8] GSE33860 [28] GSE33308 [10] GSE32598 [11] Score 8.91 9.31 9.44 9.72 10.64 10.86 11.06 11.25 11.99 12.49 12.64 13.04 13.05 13.22 13.88 14.48 14.99 15.24 15.36 15.41 16.42 16.86 17.96 18.59 18.86 19.03 19.18 19.56 20.42 21.12 21.22 21.68 21.95 22.66 22.73 23.53 23.91 23.94 24.37 25.19 25.48 25.90 26.05 27.55 27.59 27.62 27.74 28.57 28.63 28.75 1.0 Notes Symbol Num ofCEMGenes:6.Predicted183.SelectedDatasets:611.Strength:11.5 CEM 1,Geneset"[G]transportvesicle",Page4 Ccdc102a Leprel4 Rhbdf1 Abi3bp Itpripl2 Chst14 Cpxm1 Col8a1 Samd4 Plxdc2 Lamb2 Pamr1 Kank2 Timp1 Thbs3 Gulp1 S1pr3 Plod1 Emp1 Fbln1 Ttc28 Osmr Gas6 Sulf1 Bnc2 Aoc3 Thbd Tgfbi Vcan Vgll3 Selm Sdc2 Lsp1 Osr1 Ddr2 Npr2 Sdpr Flna Ndn 0.0 1.0

GSE16925 [15] GSE35785 [10]

GSE13106 [10] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE18907 [12] GSE44339 [14] GSE6383 [6] GSE14395 [24] GSE39391 [21] GSE51608 [6] GSE14354 [6] GSE40368 [10] GSE56542 [8] GSE19979 [6] GSE4193 [8] GSE53299 [6] GSE5038 [9] GSE12956 [10] GSE8044 [6] GSE12618 [6] GSE27848 [16] GSE41759 [14] GSE54349 [6] GSE40156 [42] GSE44101 [6] GSE41342 [26] GSE42601 [6] GSE26299 [108] GSE5671 [18] GSE7694 [12] GSE45820 [6] GSE23845 [15] GSE15267 [8] GSE7810 [9] GSE9013 [12] GSE13302 [30] GSE10556 [6] GSE13874 [14] GSE34618 [7] GSE11898 [9] GSE18281 [33] GSE11759 [6] GSE37191 [12] GSE48790 [8] GSE54207 [9] GSE25029 [56] GSE28277 [10] GSE18534 [15] GSE27987 [31] GSE34552 [10] GSE6210 [12] GSE16691 [12] GSE42008 [6] GSE6589 [11] GSE5037 [18] GSE35091 [11] GSE47772 [24] GSE36229 [14] GSE35396 [24] GSE9400 [8] GSE8025 [21] GSE31244 [6] GSE10813 [12] GSE35961 [12] GSE49346 [6] GSE42753 [6] GSE24625 [12] GSE26290 [12] GSE47777 [8] GSE28664 [17] GSE13044 [59] GSE13526 [6] GSE32334 [19] GSE53403 [16] GSE13408 [14] GSE39984 [18] GSE6881 [10] GSE18660 [10] GSE23408 [39] GSE27630 [8] GSE29485 [12] GSE27932 [14] GSE7069 [8] GSE32277 [33] GSE24793 [8] GSE20577 [12] GSE52550 [12] GSE22925 [14] GSE40856 [8] GSE27261 [8] GSE7342 [12] GSE27546 [51] GSE15580 [14] GSE50824 [19] GSE29813 [18] GSE15794 [6] GSE15772 [8] GSE28389 [20] GSE29766 [40] GSE17462 [8] GSE59672 [12] GSE20177 [14] GSE7020 [8] GSE13563 [6] GSE9098 [12] GSE52101 [17] GSE24295 [7] GSE8024 [8] GSE32966 [24] GSE11148 [6] GSE33134 [31] GSE30855 [6] GSE18135 [18] GSE27568 [16] GSE58307 [20] GSE11443 [6] GSE38257 [14] GSE32095 [24] GSE32937 [8] GSE29975 [6] GSE5011 [10] GSE22371 [6] GSE34091 [8] GSE31431 [34] GSE27713 [7] GSE23598 [8] GSE30852 [6] GSE43779 [6] GSE18586 [9] GSE53951 [10] GSE5245 [16] GSE10965 [8] GSE18587 [9] GSE7196 [6] GSE33471 [12] GSE12498 [12] GSE44175 [18] GSE8788 [6] GSE5333 [16] GSE4695 [6] GSE15401 [18] GSE51686 [9] GSE10113 [12] GSE16496 [102] GSE9123 [8] GSE33726 [48] GSE38224 [12] GSE45968 [6] GSE14481 [12] GSE9044 [6] GSE55162 [8] GSE24276 [6] GSE22989 [10] GSE9711 [6] GSE19793 [32] CEM+ CEM GSE15155 [12] GSE51213 [16] GSE51483 [45] GSE21576 [10] GSE52474 [154] GSE35322 [20] 0.0 GSE14088 [9] GSE22841 [12]

GSE4230 [8] Scale ofaveragePearsoncorrelations GSE19194 [14] GSE18742 [13] GSE6540 [12] GSE31106 [18] GSE42049 [8] GSE51628 [15] 0.2 GSE6867 [6] GSE36415 [14] GSE51432 [15] GSE17373 [24] GSE50439 [15] GSE30561 [6] GSE51108 [6] GSE31013 [12] GSE27302 [16] 0.4 GSE9735 [9] GSE22251 [9] GSE56777 [8] GSE59437 [30] GSE17797 [19] GSE34279 [30] GSE9892 [12] GSE30863 [20] GSE20523 [17] 0.6 GSE31598 [12] GSE53986 [16] GSE22307 [23] GSE46211 [18] GSE13963 [15] GSE13148 [10] GSE16790 [18] GSE15729 [15] GSE17817 [6] 0.8 GSE18395 [8] GSE33860 [28] GSE33308 [10] GSE32598 [11] Score 0.03 0.18 0.70 0.81 0.94 0.95 1.15 1.25 1.29 1.32 1.43 1.73 1.75 1.96 2.78 3.04 3.06 3.32 3.97 4.24 4.36 4.37 4.45 4.54 4.70 4.86 4.92 5.62 5.97 6.46 6.58 6.78 7.24 7.34 7.40 7.54 7.58 7.76 8.15 1.0 Notes GEO Series "GSE16925" 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=GSE16925 Status: Public on Aug 03 2009 Title: Expression data from mouse ES and iPS cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19672241 Summary & Design: Summary: Induced pluripotent stem (iPS) cells were produced from reprogramming of somatic cells, and they are shown to possess pluripotent properties similar to embryonic stem (ES) cells. Here we used microarrays to detail the global expression pattern among the ES cells and iPS cells, as well as the original mouse embryo fibroblast (MEF), to identify important players involved in the reprogramming process.

Overall design: Mouse ES cell cultures, as well as selected iPS cell lines and the original MEF cells they were derived from, were used for RNA extraction and hybridization on Affymetrix microarrays. Three biological replicates for each sample were processed. GeneChips were processed and data were analyzed as previously described (Zeng et al., Dev Biol 20004).

Background corr dist: KL-Divergence = 0.0695, L1-Distance = 0.0886, L2-Distance = 0.0130, Normal std = 0.6146

0.785 Kernel fit Pairwise Correlations Normal fit

Density 0.393

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

CL11-rep1CL11-rep2 (0.0455212)CL11-rep3 (0.0440412)MEF-rep1 (0.0426715)MEF-rep2 (0.125178)MEF-rep3 (0.134136)IP14D-1-rep1 (0.138402)IP14D-1-rep2 (0.0613186)IP14D-1-rep3 (0.0786587)IP14D-101-rep1 (0.0488505)IP14D-101-rep2IP14D-101-rep3 (0.0444894)IP20D-3-rep1 (0.0456856)IP20D-3-rep2 (0.063941) (0.0459365)IP20D-3-rep3 (0.0479063) (0.0332636) [ min ] [ medium ] [ max ] CEM 1 Col6a2 84.0 163.1 4086.8 P ( S | Z, I ) = 1.00 Col6a1 16.4 52.1 5454.8 Mean Corr = 0.99574 Col6a3 31.4 72.9 10545.8 Bgn 34.6 137.2 29724.3 Sspn 1.3 13.4 629.2 Crispld2 11.1 75.0 2582.8 Col1a2 2.5 28.4 30908.0 Col5a2 28.2 79.3 30475.8 Col1a1 4.8 51.7 33015.6 Col5a1 67.5 144.6 21073.5 Col3a1 1.2 24.5 6262.3 CEM 1 + Sparc 4179.7 5790.5 38415.9 Top 10 Genes Pcolce 1360.5 1988.6 22271.2 Mmp2 170.4 244.4 3696.1 Fstl1 2003.3 2738.2 27961.8 Ccdc80 3.1 21.5 9172.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE35785" 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=GSE35785 Status: Public on Apr 27 2012 Title: mRNA expression data from AG-haESC, E14 and MEF Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22541431 Summary & Design: Summary: Haploid cells are amenable for genetic analysis because they contain only one set of chromosomes.Here,we report the derivation of haESCs from androgenetic blastocysts. These cells, which we designated AG-haESCs, express classical ESC markers, are pluripotent, and contribute to various tissues including the germline upon injection into diploid blastocysts.

We used microarrays to compare the gene expression levels among androgenetic haploid embryonic stem cell lines(AG-haESC) E14 and male mouse embryonic fibroblasts (MEFs) and identified that most paternally imprinted genes were down-regulated and the maternally imprinted genes were up-regulated.

Overall design: To avoid the influence of diploidized cells on the expression profile, we collected samples from FACS of cells at G1/G0 stage by staining Hochest 33342. We used E14,which was a male embryonic stem cell lines, and MEFs isloated from male individuals as control. Gene expression profiles of all the cell lines were analysed on an Affymetrix GeneChip 430 2.0 array.

Background corr dist: KL-Divergence = 0.0603, L1-Distance = 0.0531, L2-Distance = 0.0042, Normal std = 0.6033

0.721 Kernel fit Pairwise Correlations Normal fit

Density 0.361

0.000 CEM 1

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

Pre-normalization Quantiles

AGH-OG-1AGH-OG-2 (0.0579684)AGH-EG-1 (0.058753)AGH-OG-3 (0.0648874)AGH-OG-4 (0.0913232)E14, (0.0437538) biologicalE14, biological E14,rep1 biological(0.0551784) MEF,biologicalrep2 (0.0874153) MEF,biologicalrep3 (0.154057) rep1 (0.212243) rep2 (0.174421)[ min ] [ medium ] [ max ] CEM 1 Col6a2 13.6 129.3 7087.0 P ( S | Z, I ) = 1.00 Col6a1 12.1 93.6 5463.9 Mean Corr = 0.99322 Col6a3 27.1 170.9 9939.3 Bgn 129.2 485.5 27908.5 Sspn 3.2 22.1 987.6 Crispld2 10.2 83.5 1292.5 Col1a2 80.8 557.4 28780.6 Col5a2 102.1 619.7 29303.5 Col1a1 4.3 87.3 9397.6 Col5a1 236.4 372.2 12349.3 Col3a1 16.4 54.6 8631.1 CEM 1 + Sparc 1343.5 10587.2 32149.9 Top 10 Genes Pcolce 813.1 2507.2 21915.0 Mmp2 77.0 179.7 5567.8 Fstl1 987.5 1567.8 24885.0 Ccdc80 13.8 130.3 8578.7

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE13106" 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=GSE13106 Status: Public on Sep 09 2009 Title: Regulated SMAD signalling in development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19517569 Summary & Design: Summary: Phosphorylation and subsequent nuclear translocation of SMAD proteins determine the cellular response to activin. Here we identify a novel means by which activin signalling is regulated to enable developmental stage-specific SMAD gene transcription. In response to activin A, immature proliferating mouse Sertoli cells exhibit nuclear accumulation of SMAD3, but not SMAD2, although both proteins are phosphorylated. In post-mitotic differentiating cells, both SMAD2 and SMAD3 accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; at higher concentrations maximal SMAD3 nuclear accumulation is observed, accompanied by a small, but significant, increase in nuclear SMAD2. Microarray analysis confirmed that differential SMAD utilization correlated with altered transcriptional outcomes and identified new activin target genes, Gja1 and Serpina5, which are known to be required for Sertoli cell development and male fertility. In immature Sertoli cells, genetic or transient knockdown of SMAD3 enhanced SMAD2 nuclear accumulation in response to activin, with increased Serpina5 mRNA levels associated with nuclear localized SMAD2. In transgenic mice with altered activin bioactivity that display male fertility phenotypes, testicular Gja1 and Serpina5 mRNA levels reflected altered in vivo activin levels. We conclude that regulated nuclear accumulation of phosphorylated SMAD2 is a novel determinant of developmentally regulated activin signalling.

Overall design: Murine 15dpp Sertoli Cell treated with 0ng, 5ng activin (duplicates). Total 10 samples.

Background corr dist: KL-Divergence = 0.0442, L1-Distance = 0.0746, L2-Distance = 0.0079, Normal std = 0.6871

0.677 Kernel fit Pairwise Correlations Normal fit

Density 0.339

0.000 CEM 1

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

Pre-normalization Quantiles

mus-6dpp-0ng_activin-rep1mus-6dpp-0ng_activin-rep2mus-6dpp-5ng_activin-rep1mus-6dpp-5ng_activin-rep2 (0.0847704)mus-6dpp-50ng_activin-rep1 (0.0835482)mus-6dpp-50ng_activin-rep2 (0.0864346)mus-15dpp-0ng_activin-rep1 (0.106921)mus-15dpp-0ng_activin-rep2 (0.0893667)mus-15dpp-5ng_activin-rep1 (0.0948665)mus-15dpp-5ng_activin-rep2 (0.10933) (0.135771) (0.11452) (0.0944722)[ min ] [ medium ] [ max ] CEM 1 Col6a2 849.6 5508.2 7405.2 P ( S | Z, I ) = 1.00 Col6a1 798.7 4779.8 5938.9 Mean Corr = 0.98344 Col6a3 596.4 3959.3 4338.8 Bgn 1821.3 12088.9 13832.4 Sspn 332.2 794.4 836.6 Crispld2 254.1 1322.2 1425.9 Col1a2 1131.8 8434.8 9318.8 Col5a2 482.1 4300.3 5050.0 Col1a1 608.0 4734.0 7032.6 Col5a1 562.8 3812.6 4788.1 Col3a1 212.2 1854.8 2184.3 CEM 1 + Sparc 23366.7 38989.4 40543.7 Top 10 Genes Pcolce 1527.8 12155.9 14576.7 Mmp2 464.7 3195.7 4982.7 Fstl1 1983.1 9882.2 12437.0 Ccdc80 351.2 2290.0 2451.2

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE18907" 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=GSE18907 Status: Public on Mar 19 2011 Title: Gene expression profiling of pregnant and virgin mouse lung and liver Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21646719 Summary & Design: Summary: Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.

Overall design: Three chips were done per organ (liver/lung) and per condition (virgin/pregnant), with equal amounts of RNA from two mice pooled for one chip.

Background corr dist: KL-Divergence = 0.0162, L1-Distance = 0.0642, L2-Distance = 0.0067, Normal std = 0.9265

0.431 Kernel fit Pairwise Correlations Normal fit

Density 0.215

0.000 CEM 1

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

Pre-normalization Quantiles

Lung VirginLung 1 Virgin (0.069539)Lung 2 Virgin (0.0713991)Lung 3 Pregnant (0.0727822)Lung Pregnant Lung1 (0.0736674) Pregnant Liver2 (0.0837726) Virgin Liver3 (0.0717474) 1 Virgin (0.0723684)Liver 2 Virgin (0.0667591)Liver 3 Pregnant (0.0681772)Liver Pregnant Liver1 (0.101232) Pregnant 2 (0.120014) 3 (0.128542) [ min ] [ medium ] [ max ] CEM 1 Col6a2 570.9 6633.9 13168.8 P ( S | Z, I ) = 1.00 Col6a1 301.7 3817.8 6929.3 Mean Corr = 0.98214 Col6a3 180.6 1603.6 2956.9 Bgn 4230.8 20746.8 27039.0 Sspn 66.8 998.7 1478.6 Crispld2 69.6 1856.3 2722.6 Col1a2 98.0 1645.9 2880.0 Col5a2 237.4 2931.6 3722.0 Col1a1 110.2 486.2 723.2 Col5a1 245.6 670.4 970.8 Col3a1 66.4 753.1 1482.6 CEM 1 + Sparc 3139.0 33084.2 39264.0 Top 10 Genes Pcolce 922.9 6760.8 13251.7 Mmp2 146.1 1784.4 3532.2 Fstl1 162.4 2541.4 3524.4 Ccdc80 1342.3 1597.2 2188.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE44339" 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=GSE44339 Status: Public on Jan 07 2014 Title: Identification of Ccr4-Not complex as a regulator of transition from partial to genuine iPS cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24200330 Summary & Design: Summary: Partial induced pluripotent cells (iPSCs) are cell lines strayed from normal route from somatic cells to iPSCs and are immortalized. Mouse partial iPSCs are able to convert to real iPSCs by the exposure to 2i condition using MAPK and GSK3? inhibitors. However, the molecular mechanisms of this conversion are totally not known. Our piggyback vector mediated genome-wide screen revealed that Cnot2, one of core components of Ccr4-Not complex participates in this conversion. Subsequent analyses revealed other core components, i.e., Cnot1 and Cnot3 and Trim28 which is known to extensively share genomic binding sites with Cnot3 contribute to this conversion as well. Our bioinformatics analyses indicate that the major role of these factors in the conversion is the down-regulation of developmental genes in partial iPSCs.

Overall design: Two partial iPSC clones (2B1 and 5C5) cultured under conventional culture condition with leukemia inhibitory factor (LIF) and serum and those converted to iPSCs by the exposure to 2i condition were used for RNA source. Partial iPSCs (2B1) cultured under conventional condition in which either one of Cnot1, Cnot2, Cnot3 and Trim28 cDNA or these factors were combinatorially incorporated after retrovirus infection and those in which empty vector or Nanog were stably integrated were also used for RNA source. In addition, embryonic fibroblasts and embryonic stem cells (ESCs) from 13.5 dpc embryos and blastocysts, respectively, from Nanog-GFP transgenic mice and wild-type ESC line (EBRTcH3) were used for RNA source.

Background corr dist: KL-Divergence = 0.0869, L1-Distance = 0.0318, L2-Distance = 0.0019, Normal std = 0.4775

0.835 Kernel fit Pairwise Correlations Normal fit

Density 0.418

0.000 CEM 1

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

Pre-normalization Quantiles

Partial iPSCsPartial (2B1) iPSCsiPSCs untreated (5C5)fromiPSCs 2B1untreated from (0.0804541)Nanog-GFP with 5C5 2i (0.0372077)Nanog-GFP treatmentwith MEFs 2iWild-type treatment from(0.0419089) ESCsPartial 12.5 ESCs from(0.044674) dpc iPSCsPartial blastocyst(EBRTcH3) embryo (2B1) iPSCsPartial (0.266287) with(0.110447) (0.0999323) (2B1) iPSCsPartial empty with (2B1) iPSCsPartial vector Cnot1 with (2B1) iPSCsPartial (0.0606492)(0.0499914) Cnot2 with (2B1) iPSCsPartial (0.0418441) Cnot3 with (2B1) iPSCs (0.0455532) Trim28 with (2B1) Cnot1,2,3(0.0487132) with Nanog (0.0364522)[ (0.0358855)min ] [ medium ] [ max ] CEM 1 Col6a2 116.3 269.1 9383.3 P ( S | Z, I ) = 1.00 Col6a1 31.1 236.3 8839.3 Mean Corr = 0.97809 Col6a3 45.2 307.1 13400.2 Bgn 48.6 1326.0 30664.9 Sspn 16.3 114.9 711.5 Crispld2 37.5 59.1 722.4 Col1a2 18.1 80.9 17241.0 Col5a2 25.8 370.9 24570.0 Col1a1 29.4 66.1 12398.9 Col5a1 63.8 158.5 12402.2 Col3a1 13.4 17.8 3385.1 CEM 1 + Sparc 775.5 3245.2 20080.2 Top 10 Genes Pcolce 1846.7 7017.8 20634.9 Mmp2 130.0 358.9 4130.4 Fstl1 1884.7 10458.9 18214.0 Ccdc80 46.4 292.4 9767.0

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE6383" 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=GSE6383 Status: Public on Mar 12 2007 Title: Mouse small intestine epithelium vs. mesenchyme Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17299133 Summary & Design: Summary: During organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.

Keywords: comparative genomic hybridization: epithelium vs. mesenchyme

Overall design: Mouse small intestine (E18.5) is separated to epithelium and mesenchyme. Total RNA is extracted from epithelium and mesenchyme. There are 6 samples in this microarray experiment: 3 for epithelium and 3 for mesenchyme. Samples are hybridized the affymetrix Mouse Genome 430 2.0 Array. We compare the gene expression between epithelium and mesenchyme to study the gene expression profiles in these two compartments.

Background corr dist: KL-Divergence = 0.0057, L1-Distance = 0.0149, L2-Distance = 0.0002, Normal std = 0.9832

0.414 Kernel fit Pairwise Correlations Normal fit

Density 0.207

0.000 CEM 1

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

Pre-normalization Quantiles

small intestinesmall intestine smallEPI-MES intestine smallEPI-MES Epi intestineA small EPI-MES(0.133224) Epi intestineB small Mes(0.206253) Epi A intestineC (0.167051) Mes(0.15109) B (0.164173) Mes C (0.178209)[ min ] [ medium ] [ max ] CEM 1 Col6a2 638.4 12828.1 15097.2 P ( S | Z, I ) = 1.00 Col6a1 220.6 10477.4 11441.5 Mean Corr = 0.97621 Col6a3 441.1 8510.3 9293.4 Bgn 311.9 3704.3 4231.7 Sspn 56.4 701.8 880.4 Crispld2 248.7 748.1 1245.1 Col1a2 142.8 8671.1 9721.9 Col5a2 366.6 5238.7 6874.4 Col1a1 89.6 12035.3 15097.2 Col5a1 120.9 5984.5 7548.6 Col3a1 48.0 4887.9 5209.8 CEM 1 + Sparc 441.1 14086.2 14817.2 Top 10 Genes Pcolce 297.8 4560.5 5209.8 Mmp2 277.9 3948.3 5337.7 Fstl1 79.8 6571.4 6912.5 Ccdc80 225.7 1985.1 2167.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE14395" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 24 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14395 Status: Public on Sep 11 2009 Title: Gender-specific gene repression of PPAR-alpha KO mice in liver and heart Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19729835 Summary & Design: Summary: Most metabolic studies are conducted in male animals; thus, the molecular mechanism controlling gender-specific pathways has been neglected, including sex-dependent responses to peroxisome proliferator-activated receptors (PPARs). Here we show that PPARalpha has broad female-dependent repressive actions on hepatic genes involved in steroid metabolism and inflammation. In males, this effect is reproduced by the administration of synthetic PPARalpha ligand. Using the steroid hydroxylase gene Cyp7b1 as a model, we elucidated the molecular mechanism of this PPARalpha-dependent repression. Initial sumoylation of the ligand-binding domain of PPARalpha triggers the interaction of PPARalpha with the GA-binding protein alpha bound to the target promoter. Histone deacetylase is then recruited, and histones and adjacent Sp1-binding site are methylated. These events result in the loss of Sp1-stimulated expression, and thus the down-regulation of Cyp7b1. Physiologically, this repression confers protection against estrogen-induced intrahepatic cholestasis, paving the way for a novel therapy against the most common hepatic disease during pregnancy.

Keywords: Genetic modification

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

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

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

Liver_male_WT_pool1Liver_male_WT_pool2Liver_male_WT_pool3 Liver_male_KO_pool4(0.0296596) Liver_male_KO_pool5(0.0388107) Liver_male_KO_pool6(0.0311484) Liver_female_WT_pool7(0.0399029) Liver_female_WT_pool8(0.0356291) Liver_female_WT_pool9(0.0428447)Liver_female_KO_pool10 (0.0327644)Liver_female_KO_pool11 (0.0399386)Liver_female_KO_pool12 (0.0377513)Heart_male_WT_pool1 (0.031723)Heart_male_WT_pool2 (0.0389333)Heart_male_WT_pool3 (0.079655)Heart_male_KO_pool4 (0.03932)Heart_male_KO_pool5 (0.0298545)Heart_male_KO_pool6 (0.0542703)Heart_female_WT_pool7 (0.0379702)Heart_female_WT_pool8 (0.0479128)Heart_female_WT_pool9 (0.0457919)Heart_female_KO_pool10 (0.040355)Heart_female_KO_pool11 (0.043185)Heart_female_KO_pool12 (0.0383289) (0.0426151) (0.039277) (0.0623583)[ min ] [ medium ] [ max ] CEM 1 Col6a2 313.8 2841.6 3904.2 P ( S | Z, I ) = 1.00 Col6a1 132.7 1597.9 2313.1 Mean Corr = 0.97356 Col6a3 153.9 701.0 1288.2 Bgn 3026.8 7070.0 9012.6 Sspn 121.0 9446.0 11121.1 Crispld2 120.6 931.0 1498.4 Col1a2 116.7 688.4 1397.8 Col5a2 110.6 446.4 700.1 Col1a1 132.9 1686.9 2950.1 Col5a1 153.2 803.5 1195.9 Col3a1 92.3 115.7 136.1 CEM 1 + Sparc 1102.9 12892.8 16894.5 Top 10 Genes Pcolce 178.1 3365.7 4286.0 Mmp2 124.5 1315.5 1860.7 Fstl1 130.5 1855.6 2686.2 Ccdc80 261.5 2669.8 3545.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE39391" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 21 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39391 Status: Public on Aug 30 2012 Title: Gene expression data from ahES cells, ES cells, MEF cells and round sperm Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23023130 Summary & Design: Summary: Haploid stem cells offer an easy-to-manipulate genetic system and therefore have great values for studies of recessive phenotypes. Here, we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ-layers in vitro and in vivo, and contribute to germline of chimeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte injection procedure can also produce viable transgenic mice from genetically engineered ahES cells.

We used microarrays to compare the global programme of gene expression among ahES cells, normal diploid ES cells, MEF cells and round sperm cells and found that gene expression pattern of ahES cells was highly similar with ES cells but was distinct from MEF cells and round sperms.

Overall design: Androgenetic haploid ES cells were FACS sorted to harvest the G0/G1 phase haploid cells. Total RNA were extracted from three ahES cell lines (AH129-5, AH129-N1, AH129-NC1, all 129Sv genetic background), two ES cell lines ( CS1-1, R1, 129Sv background), MEF cells and round sperm and hybridized with Affymetrix GeneChip 430 2.0 array. Data were collected and analyzed to compare their gene expression pattern.

Background corr dist: KL-Divergence = 0.0710, L1-Distance = 0.0949, L2-Distance = 0.0148, Normal std = 0.6873

0.712 Kernel fit Pairwise Correlations Normal fit

Density 0.356

0.000 CEM 1

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

Pre-normalization Quantiles

AH129-5,AH129-5, biologicalAH129-5, biological rep1AH129-N1,biological biological(0.03364) rep2AH129-N1,biological (0.0284922) rep3AH129-N1,biological (0.0311383) rep1AH129-NC1, (0.0333755) rep2AH129-NC1, (0.0227699) biological rep3AH129-NC1, (0.0463272) biologicalCS1-1, rep1 biological(0.0196757) biologicalCS1-1, rep2 (0.0199953) biologicalCS1-1, rep3 rep1 (0.0189494) biologicalR1,(0.0363476) rep2 biological R1,(0.022504) rep3 biological rep1 R1,(0.021496) biological(0.0228651) rep2MEF, (0.0313657) biological rep3MEF, (0.0238971) biologicalMEF, rep1 biological(0.0963175)round rep2 (0.0921787)sperm,round rep3 (0.0949898)sperm,biologicalround sperm,biological rep1 biological(0.115834) rep2 (0.0838129) rep3 (0.104028)[ min ] [ medium ] [ max ] CEM 1 Col6a2 31.2 205.6 8577.8 P ( S | Z, I ) = 1.00 Col6a1 35.2 191.7 8573.9 Mean Corr = 0.97057 Col6a3 78.6 495.3 17164.6 Bgn 10.0 1203.1 27503.8 Sspn 1.7 18.8 136.4 Crispld2 5.3 45.2 1573.5 Col1a2 3.0 1802.0 18802.9 Col5a2 5.2 2821.1 25901.1 Col1a1 10.8 386.4 8168.4 Col5a1 199.9 1963.8 15474.2 Col3a1 4.9 330.2 1582.8 CEM 1 + Sparc 28.7 8009.1 32879.5 Top 10 Genes Pcolce 1280.5 2470.8 17991.6 Mmp2 3.7 253.6 3505.0 Fstl1 42.4 2309.5 21044.4 Ccdc80 6.9 778.1 5366.3

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE51608" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.518 Kernel fit Pairwise Correlations Normal fit

Density 0.259

0.000 CEM 1

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

Pre-normalization Quantiles

Ebf2+ rep1Ebf2+ (0.243427) rep2Ebf2+ (0.162302) rep3Ebf2- (0.142128) rep1Ebf2- (0.168191) rep2Ebf2- (0.149488) rep3 (0.134465) [ min ] [ medium ] [ max ] CEM 1 Col6a2 1574.9 43227.8 50350.2 P ( S | Z, I ) = 1.00 Col6a1 1434.6 35256.1 41170.8 Mean Corr = 0.96912 Col6a3 964.2 39229.0 40541.4 Bgn 3480.4 28747.3 34338.0 Sspn 79.9 2013.9 2953.6 Crispld2 179.1 5321.7 7453.4 Col1a2 1546.5 25246.7 29005.1 Col5a2 1267.7 39227.6 46007.4 Col1a1 119.1 2943.0 3482.9 Col5a1 2784.6 15710.6 18408.4 Col3a1 173.4 19437.8 20253.8 CEM 1 + Sparc 901.1 20659.1 37582.3 Top 10 Genes Pcolce 1302.7 54546.7 59581.4 Mmp2 399.8 26644.0 30475.9 Fstl1 2438.5 29661.5 35190.0 Ccdc80 897.3 20643.9 23847.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE14354" 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=GSE14354 Status: Public on Jan 13 2009 Title: Testicular germ cell tumor susceptibility genes from the consomic 129.MOLF-Chr19 mouse strain Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17671812 Summary & Design: Summary: Chromosome substitution strains (CSS or consomic strains) are useful for mapping phenotypes to chromosomes. However, huge efforts are needed to identify the gene(s) responsible for the phenotype in the complex context of the chromosome. Here, we report the identification of candidate disease genes from a CSS using a combination of genetic and genomic approaches as well as by using knowledge about the germ cell tumor disease etiology. We utilized the CSS, 129.MOLF-Chr 19 chromosome substitution strain (or M19), in which males develop germ cell tumors of the testes at an extremely high rate. We are able to identify 3 protein-coding genes and 1 microRNA on chromosome 19 that have previously not been implicated to be testicular tumor susceptibility genes. Our findings suggest that changes in gene expression levels in the gonadal tissues of multiple genes from Chr 19 likely contribute to the high TGCT incidence of the M19 strain. Our data advances the use of CSS to identify disease susceptibility genes and demonstrates that the 129.MOLF-Chr 19 strain serves as a useful model to elucidate the genetics and biology of germ cell transformation and tumor development.

Overall design: By analyzing the data of differentially expressed genes present in the 3 samples, as well as selecting those that map to Chr 19, we were able to exclude a majority of the genes but found 3 genes in common. The 3 genes map to Chr 19 and were found to be downregulated in the M19 strain E13.5 and PN1 gonads as well as E13.5 embryos. These are Zfp162, D19Bwg1357e and Cox15. These 3 genes have not been previously implicated in testicular tumorigenesis and are novel TGCT candidate susceptibility genes.

Background corr dist: KL-Divergence = 0.0269, L1-Distance = 0.0112, L2-Distance = 0.0001, Normal std = 0.6813

0.586 Kernel fit Pairwise Correlations Normal fit

Density 0.293

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 MouseE13.5 testis_129/SvMouseE13.5 testis_M19maleE13.5 embryos_129/Sv (0.0917496) malePN1 (0.217424) embryos_M19 MousePN1 testis_129/SvMouse (0.172662) (0.141852) testis_M19 (0.157431) (0.218882)[ min ] [ medium ] [ max ] CEM 1 Col6a2 1748.1 4687.2 9084.7 P ( S | Z, I ) = 1.00 Col6a1 1254.3 3048.9 7138.8 Mean Corr = 0.96652 Col6a3 1271.0 1398.8 1655.9 Bgn 2619.9 6009.1 9141.9 Sspn 211.0 408.9 574.4 Crispld2 418.5 582.4 848.2 Col1a2 3866.0 4578.8 8062.2 Col5a2 2202.8 2708.1 3678.7 Col1a1 5857.9 6859.4 10314.2 Col5a1 1660.3 2212.8 2689.2 Col3a1 1675.2 2664.2 2732.4 CEM 1 + Sparc 9507.7 13872.1 20681.6 Top 10 Genes Pcolce 834.5 3328.9 5037.4 Mmp2 1296.5 3487.7 3942.2 Fstl1 4373.6 5740.2 7735.2 Ccdc80 683.3 1171.0 1228.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE40368" 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=GSE40368 Status: Public on Aug 09 2013 Title: Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23637227 Summary & Design: Summary: Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.

Overall design: Comparison of KO vs. WT with five replications per treatment sample

Background corr dist: KL-Divergence = 0.0632, L1-Distance = 0.0318, L2-Distance = 0.0018, Normal std = 0.5180

0.770 Kernel fit Pairwise Correlations Normal fit

Density 0.385

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

RProia1_1_LA_Mouse430_2_1_1WT-undRProia10_10_LA_Mouse430_2_10_10KO-undRProia2_2_LA_Mouse430_2_2_2WT-undRProia3_3_LA_Mouse430_2_3_3WT-undRProia4_4_LA_Mouse430_2_4_4WT-undRProia5_5_LA_Mouse430_2_5_5WT-und (0.288842)RProia6_21_LA_Mouse430_2_6_21KO-undRProia7_23_LA_Mouse430_2_7_23KO-und (0.0624782) (0.094782)RProia8_8_LA_Mouse430_2_8_8KO-und (0.127863)RProia9_9_LA_Mouse430_2_9_9KO-und (0.0707466) (0.0797345) (0.0754153) (0.0729033)[ min (0.0793378) (0.0478975)] [ medium ] [ max ] CEM 1 Col6a2 244.8 634.1 3872.7 P ( S | Z, I ) = 1.00 Col6a1 164.5 547.5 3178.2 Mean Corr = 0.96318 Col6a3 89.4 309.9 1813.3 Bgn 273.0 966.0 9210.8 Sspn 37.5 46.3 139.2 Crispld2 55.3 79.3 577.3 Col1a2 223.0 581.8 5881.6 Col5a2 260.9 455.9 4516.2 Col1a1 1304.4 2666.1 19363.0 Col5a1 393.1 657.3 5600.0 Col3a1 12.9 18.8 110.8 CEM 1 + Sparc 3735.8 5295.1 18349.0 Top 10 Genes Pcolce 72.6 119.7 778.8 Mmp2 34.7 84.1 199.9 Fstl1 95.5 560.9 2875.0 Ccdc80 97.0 159.9 2082.2

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE56542" 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=GSE56542 Status: Public on Apr 07 2014 Title: Expression data from CD4+ T cells of germ free mice, SPF IQI mice and SPF C57BL/6 mice depletd with Uhrf1 (by Cd4Cre-Uhrf1flox/flox) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Commensal bacteria shapes gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms has not yet been unknown. To reveal the mechanism, we isolated Treg cells and Non-Treg cells and performed the global expression analysis.

Overall design: Colonic lamina propria cells were isolated from mice described above. Treg cells and Non-Treg cells (also called as Tconv cells) were sorted by FACS AriaIII

Background corr dist: KL-Divergence = 0.0404, L1-Distance = 0.0306, L2-Distance = 0.0014, Normal std = 0.6162

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

SPF TregSPF (0.129497) TconvGF Treg(0.192129)GF (0.119725) TconvUhrf1 (0.116301) +/+Uhrf1 Tconv +/+Uhrf1 (0.104049) Treg fl/fl (0.128488)Uhrf1 Tconv fl/fl (0.0909353) Treg (0.118875) [ min ] [ medium ] [ max ] CEM 1 Col6a2 4.6 116.7 1838.6 P ( S | Z, I ) = 1.00 Col6a1 15.1 124.0 2035.1 Mean Corr = 0.95978 Col6a3 3.0 42.4 1084.5 Bgn 11.9 168.0 2916.1 Sspn 1.7 13.1 37.5 Crispld2 26.4 45.3 165.4 Col1a2 17.3 181.1 2983.4 Col5a2 1.0 28.5 969.6 Col1a1 15.8 136.8 2095.7 Col5a1 14.8 83.9 542.6 Col3a1 7.7 180.6 4479.6 CEM 1 + Sparc 11.3 202.5 2672.2 Top 10 Genes Pcolce 23.8 70.3 1042.2 Mmp2 12.2 26.6 218.8 Fstl1 3.7 50.0 681.3 Ccdc80 5.5 51.8 411.0

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE19979" 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=GSE19979 Status: Public on Jan 22 2010 Title: Gene expression profiles of P7 bladder epithelium compartments isolated from Upk1b mice. (GUDMAP Series ID: 34) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing genitourinary tract The central thesis is straightforward. The combination of microdissected tissues and FACS sorted cells plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here delineates the gene expression profiles of the epithelial compartments of the P7 mouse bladder.

Overall design: At postnatal day 7 mice were euthanized by CO2 asphyxiation and the bladders were removed and cut at the bladder neck. The bladder was cut into rings and treated with 1 mg/ml trypsin in Tyrode’s solution for 30 minutes at 37 ´C. The layers were separated by gentle microdissection and the epithelial layer was further digested in a mixture of Blendzymes 1 & 4 at 37 ´C until a single cell suspension was obtained. The samples were placed in RLT and stored at -80 ´C.RNA was prepared and the Epicentre 2-round amplification scheme described under the Lessard Group Protocols on the GUDMAP pages were performed. The Affymetrix GeneChip Mouse Genome 430 2.0 Array was used to interrogate the amplified RNA.

Background corr dist: KL-Divergence = 0.0264, L1-Distance = 0.0357, L2-Distance = 0.0018, Normal std = 0.7181

0.556 Kernel fit Pairwise Correlations Normal fit

Density 0.278

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

uroplakin1-veuroplakin2-ve (0.177846)uroplakin5-ve (0.213536)uroplakin1+ve (0.207204)uroplakin2+ve (0.182616)uroplakin5+ve (0.143635) (0.0751628) [ min ] [ medium ] [ max ] CEM 1 Col6a2 114.1 31235.4 61465.1 P ( S | Z, I ) = 1.00 Col6a1 94.8 27880.0 42389.6 Mean Corr = 0.95926 Col6a3 158.8 33468.2 49894.1 Bgn 144.0 25415.4 29491.1 Sspn 11.2 1195.5 1841.2 Crispld2 55.0 6255.4 8597.4 Col1a2 542.2 53750.7 119869.2 Col5a2 147.9 35042.2 58442.8 Col1a1 44.2 2919.0 10276.2 Col5a1 139.7 28584.7 56989.2 Col3a1 160.1 34364.4 51096.1 CEM 1 + Sparc 173.6 19543.6 52015.2 Top 10 Genes Pcolce 235.1 26692.2 62102.9 Mmp2 118.4 30689.8 42030.3 Fstl1 37.6 16278.7 31360.7 Ccdc80 244.8 4517.6 9077.2

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE4193" 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=GSE4193 Status: Public on Feb 09 2006 Title: Gene expression in murine germ cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 16581510 Summary & Design: Summary: In mammals, the X and Y chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during prophase I in the male germline, but their status thereafter is currently unclear. An abundance of X-linked spermatogenesis genes has spawned the view that the X must be active [1-8]. On the other hand, the idea that the imprinted paternal X of the early embryo may be pre-inactivated by MSCI suggests that silencing may persist longer [9-12]. To clarify this issue, we establish a comprehensive X-expression profile during mouse spermatogenesis. Here, we discover that the X and Y occupy a novel compartment in the post-meiotic spermatid and adopt a non-Rabl configuration. We demonstrate that this post-meiotic sex chromatin (PMSC) persists throughout spermiogenesis into mature sperm and exhibits epigenetic similarity to the XY body. In the spermatid, 87% of X-linked genes remain suppressed post-meiotically, while autosomes are largely active. We conclude that chromosome-wide X-silencing continues from meiosis to the end of spermiogenesis and discuss implications for proposed mechanisms of imprinted X-inactivation.

Keywords: Specific germ cells from murine testis

Overall design: Independent germ cell preps were used for array analysis. Duplicates were provided for each sample.

Background corr dist: KL-Divergence = 0.0209, L1-Distance = 0.0329, L2-Distance = 0.0015, Normal std = 0.7625

0.523 Kernel fit Pairwise Correlations Normal fit

Density 0.262

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

Type A Typespermatogonia A Typespermatogonia B Typespermatogonia replicate B Pachytenespermatogonia replicate 1 (0.131805)Pachytene replicate 2 spermatocytes (0.124587)Round replicate 1 spermatocytes (0.142695) spermatidsRound 2 replicate(0.12879) spermatids replicate 1 (0.107518) replicate 12 (0.114357)(0.131852) 2 [(0.118397) min ] [ medium ] [ max ] CEM 1 Col6a2 368.4 4011.9 7910.6 P ( S | Z, I ) = 1.00 Col6a1 113.8 4341.2 7358.0 Mean Corr = 0.95867 Col6a3 294.4 1380.5 2833.0 Bgn 293.4 1755.1 4997.3 Sspn 64.6 362.6 563.1 Crispld2 102.6 632.5 920.6 Col1a2 58.5 5837.6 10418.6 Col5a2 61.4 699.1 2159.5 Col1a1 8.4 4853.8 7141.7 Col5a1 154.3 1864.2 2919.8 Col3a1 23.3 1304.7 3899.3 CEM 1 + Sparc 1205.2 17351.5 19341.4 Top 10 Genes Pcolce 538.0 3711.1 6809.3 Mmp2 67.3 1238.1 2528.3 Fstl1 110.3 3481.7 7033.9 Ccdc80 74.6 647.7 1290.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE53299" 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=GSE53299 Status: Public on Mar 08 2014 Title: Expression data from mouse protein iPS cells compared to mouse embryonic stem cells and mouse hepatocyte. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Increased genomic integrity an improved protein-based iPS cell method compared to current viral induced strategies

We used microarrays to detail the global gene expression of protein-based iPS cells

Overall design: Total RNAs were prepared from mH, mES, miPS cells usingTRIzol reagent (Invitrogen, Carlsbad, CA) and their cDNAs were allowed to hybridize to Affymetrix Mouse Expression Array 430 containing over 43,000 mouse transcripts at the Harvard Partners Center for Genomics and Genetics.

Background corr dist: KL-Divergence = 0.0349, L1-Distance = 0.0396, L2-Distance = 0.0020, Normal std = 0.7013

0.596 Kernel fit Pairwise Correlations Normal fit

Density 0.298

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

protein proteinbased mouse proteinbased iPSmouse proteinbased line iPSmouse mouse1based (0.0784774) line iPSmouseembryonicmouse2 (0.188432) line iPShepatocyte3 (0.0673456) linestem 4 cell(0.141155) primary (0.114391) culture[ min (0.410199) ] [ medium ] [ max ] CEM 1 Col6a2 25.0 173.4 4908.2 P ( S | Z, I ) = 1.00 Col6a1 87.4 130.7 3351.0 Mean Corr = 0.95607 Col6a3 4.1 174.0 4895.2 Bgn 242.1 1095.4 23099.0 Sspn 6.6 36.7 181.4 Crispld2 72.1 119.4 662.4 Col1a2 6.4 94.5 11076.5 Col5a2 84.8 216.4 16183.7 Col1a1 9.7 57.4 5567.0 Col5a1 272.6 680.3 7898.5 Col3a1 22.3 39.8 2164.6 CEM 1 + Sparc 5244.2 6719.0 26748.5 Top 10 Genes Pcolce 3673.7 5615.6 12931.4 Mmp2 262.8 580.1 2311.2 Fstl1 2172.7 2921.5 17086.6 Ccdc80 7.2 59.8 1994.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE5038" 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=GSE5038 Status: Public on Jun 09 2006 Title: zhang-affy-mouse-308606 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: In our original grant we proposed to use the NR3B-null mouse model to study the role of NR3B subunit in motor neuron function. We have now successfully generated NR3B null mice. Interestingly, NR3B-null mice invariably die at age P4-P8. Our preliminary examination indicates that the motor strength of these mice is severely impaired prior to death. As we continue to explore the cause of death in NR3B null mice, we propose to conduct gene profiling experiments to search for transcription changes in the brain related to ablation of the NR3B gene. We have used the facility provided by the NINDS/NIMH Microarray Consortium to identify genes that show abnormal expression patterns in these mice. We would like to compare these changes with that opccured in SOD1 mice, a mouse model of motor neuron diseases. Analysis of these genes will help to identify changes in networks and pathways that may cause the death of NR3B-null mice. These studies will further help to elucidate the functional role of NR3B in motor neurons.

We will compare samples from motor neurons of wild type and SOD1 mice to identify genes that show abnormal expression patterns, which may be implicated in the death of SOD1 mice and shared with the same changes in NR3B-null mice.

We hypothesize that genes with their transcription level changing significantly in SOD1 mutant mice will be associated with the molecular mechanism underlying the death of motor neurons.

We like to compare motor neuron and spinal cord smaples from SOD1 mice at the age prior to the disease onset. Total RNA from total 9 samples will be purified, each from ~200 motor neurons obtained by Laser Capture Microdissection and the total spinal cord. Extracted RNAs will be subjected to one or two rounds of amplification and the obtained cRNA will be biotinylated. The purified cRNA will be sent to the NINDS/NIMH Microarray Consortium be used to hybridize the GeneChip Mouse Genome 430 2.0 Array. The hybridization, scanning, and initial data analysis of these GeneChips will be conducted by the Consortium staff. We will analyze the collected data further after data collection. We will first identify genes that show significant changes between wild-type and SOD1 mice and then compare that with the result from NR3B null mice.

Keywords: other

Overall design:

Background corr dist: KL-Divergence = 0.0309, L1-Distance = 0.0667, L2-Distance = 0.0062, Normal std = 0.7668

0.589 Kernel fit Pairwise Correlations Normal fit

Density 0.294

0.000 CEM 1

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

Pre-normalization Quantiles

spinal cord,spinal ventral cord,spinal ventralspinal cord,spinal cord: ventralspinal cord,spinal D28WTSP1 cord: ventralspinal cord,spinal D28WTSP2 cord: ventralspinal cord,e1spinal le1D28WTSP3_e1_le1 cord: ventralspinal (0.187643) cord,e1_le1spinal D28WTMN1_e1_le1 cord: ventralspinal (0.147957)cord,spinal D28WTMN2_e1_le1 cord: ventralspinal cord,(0.143234) D28WTMN3_e1_le1 cord: ventralspinal (0.0877513) D28SDMN1_e1_le1 cord: spinal (0.0896579) D28SDMN2_e1_le1 cord: (0.0715947)[ D28SDMN3_e1_le1min (0.0977489) ] (0.0962313) (0.0781817)[ medium ] [ max ] CEM 1 Col6a2 18.4 69.1 1236.3 P ( S | Z, I ) = 1.00 Col6a1 11.5 64.3 1090.6 Mean Corr = 0.95473 Col6a3 76.5 129.6 832.9 Bgn 2.7 51.7 1605.8 Sspn 23.9 162.5 1296.6 Crispld2 4.2 13.9 449.0 Col1a2 3.5 61.7 3581.3 Col5a2 10.7 78.4 1269.3 Col1a1 1.7 4.2 1342.7 Col5a1 70.8 387.0 481.9 Col3a1 10.9 42.7 539.8 CEM 1 + Sparc 2808.4 3452.3 21677.8 Top 10 Genes Pcolce 0.4 32.8 1996.4 Mmp2 17.5 51.4 774.6 Fstl1 2602.3 12728.0 14281.2 Ccdc80 215.6 372.9 992.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE12956" 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=GSE12956 Status: Public on Feb 26 2010 Title: Arx acts as a key selector gene of the ventral telencephalon mainly through its repression transcriptional activity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23968833 Summary & Design: Summary: The homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.

Overall design: Three timed-pregnant Arx heterozygous dams crossed with C57Bl/6 males were sacrificed at E14.5, the embryos harvested and placed into cold PBS. After brain isolarion, meninges and olfactory bulbs were removed, and the ventral telencephalon separated from the overlying cerebral cortex. The same procedure was repeated for 5 wt and 5 Arx mutant embryos.

Background corr dist: KL-Divergence = 0.0837, L1-Distance = 0.0242, L2-Distance = 0.0009, Normal std = 0.4661

0.856 Kernel fit Pairwise Correlations Normal fit

Density 0.428

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 ARX wt1 (0.110984) ARX wt2 (0.101002) ARX wt5 (0.0946246) ARX wt21 ARX(0.123666) mut22 (0.0775236) ARXmut 11 ARX(0.118288)mut 12 ARX(0.0824916)mut 13 ARX(0.0833584)mut 14 ARX(0.121408) 15 (0.0866539) [ min ] [ medium ] [ max ] CEM 1 Col6a2 166.5 931.6 1259.8 P ( S | Z, I ) = 1.00 Col6a1 63.8 414.1 490.9 Mean Corr = 0.95332 Col6a3 60.7 321.9 421.3 Bgn 348.9 1249.2 1554.7 Sspn 43.6 110.6 151.1 Crispld2 36.3 59.1 72.6 Col1a2 27.7 914.1 1302.0 Col5a2 492.0 1528.0 1856.4 Col1a1 35.8 640.1 1320.9 Col5a1 253.9 486.2 679.1 Col3a1 21.1 403.9 633.4 CEM 1 + Sparc 2609.1 5076.9 6545.9 Top 10 Genes Pcolce 55.9 309.4 408.7 Mmp2 68.6 236.6 321.0 Fstl1 1669.0 2847.8 3521.4 Ccdc80 363.3 457.7 558.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE8044" 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=GSE8044 Status: Public on Jun 08 2007 Title: Brown versus white tissue adipose selective genes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17618855 Summary & Design: Summary: The aim of this study was to identify genes expressed selectively in brown adipose tissue as compared to white adipose tissue from the same animals. This analysis provides a gene set that is brown and white adipose selective.

Keywords: tissue comparison from mice

Overall design: Interscapular brown adipose tissue and epididymal white adipose tissue was carefully dissected from 3 male C57Bl/6 mice. These samples were profiled independently using Affymetrix mouse 430_2 gene arrays, representing 3 biological replicates for each brown and white adipose tissues.

Background corr dist: KL-Divergence = 0.0069, L1-Distance = 0.0138, L2-Distance = 0.0002, Normal std = 0.9444

0.428 Kernel fit Pairwise Correlations Normal fit

Density 0.214

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 adiposeWhite adipose adultWhite rep1 adipose adultBrown (0.150127) rep2 adiposeadultBrown (0.167029) rep3 adiposeBrown adult (0.15255) rep1 adipose adult (0.132463) rep2 adult (0.205454) rep3 (0.192378)[ min ] [ medium ] [ max ] CEM 1 Col6a2 1737.7 7947.8 10563.5 P ( S | Z, I ) = 1.00 Col6a1 2849.5 8817.4 11583.3 Mean Corr = 0.94948 Col6a3 2060.0 5085.9 6719.5 Bgn 2663.7 10745.6 14022.5 Sspn 1144.1 1611.5 1790.5 Crispld2 209.9 709.4 767.5 Col1a2 1568.0 4489.2 5817.7 Col5a2 1526.1 6254.9 7655.2 Col1a1 2486.8 6599.5 10045.6 Col5a1 1230.2 4930.9 5596.2 Col3a1 830.1 3687.9 4000.5 CEM 1 + Sparc 13182.3 23684.7 25638.5 Top 10 Genes Pcolce 1610.7 2682.0 2954.8 Mmp2 1116.7 1538.3 1699.4 Fstl1 845.8 5642.7 7218.0 Ccdc80 1681.2 18623.5 19937.4

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE12618" 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=GSE12618 Status: Public on Jan 16 2009 Title: Gene expression profiles of E13 bladder compartments. (GUDMAP Series ID: 24) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The long term objective is to create an encyclopedia of the expression levels of all genes in multiple components of the developing bladder. The central thesis is straightforward. The combination of microdissected tissues and FACS sorted cells plus microarray analysis offers a powerful, efficient and effective method for the creation of a global gene expression atlas of the developing urogenital system. Microarrays with essentially complete genome coverage can be used to quantitate expression levels of every gene. The ensuing rapid read-out provides an expression atlas that is more sensitive, more economical and more complete than would be possible by in situ hybridizations alone. The data submitted here delineates the gene expression profiles of the mesenchymal and epithelial compartments of the e13 mouse bladder.

Keywords: Mouse embryonic day 13 bladder mesenchyme and epithelium.

Overall design: FVB/N mice were time mated. At embryonic day 13 mice were euthanized by decapitation and the bladders were microdissected, cut just above the ureters, and treated with 20 ´M EDTA for 20 minutes. Mesenchymal and epithelial compartments were then separated by rimming the bladder with a needle and harvested in RLT. Total RNA was isolated for gene expression analysis using the Affymetrix MOE430 microarray chip

Background corr dist: KL-Divergence = 0.0343, L1-Distance = 0.0395, L2-Distance = 0.0022, Normal std = 0.6718

0.608 Kernel fit Pairwise Correlations Normal fit

Density 0.304

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

mesenchyme1mesenchyme2 mesenchyme4(0.221669) urothelium5(0.142683) urothelium7(0.164853) (0.177855)urothelium8 (0.156908) (0.136031) [ min ] [ medium ] [ max ] CEM 1 Col6a2 88.2 2453.9 5149.8 P ( S | Z, I ) = 1.00 Col6a1 55.4 1676.9 3368.4 Mean Corr = 0.94834 Col6a3 164.9 4082.9 6361.1 Bgn 194.7 3807.4 5744.3 Sspn 17.5 654.6 855.9 Crispld2 11.3 2103.6 3215.7 Col1a2 320.0 17941.1 39110.2 Col5a2 696.6 12563.0 15520.0 Col1a1 10.0 415.3 914.1 Col5a1 704.8 7437.8 12950.3 Col3a1 156.1 8419.1 14421.3 CEM 1 + Sparc 131.9 939.1 3744.2 Top 10 Genes Pcolce 211.4 4159.4 4714.7 Mmp2 162.7 6899.7 9854.0 Fstl1 666.7 6826.5 10087.8 Ccdc80 622.6 5015.6 7246.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE27848" 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=GSE27848 Status: Public on Oct 02 2011 Title: Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23239972 Summary & Design: Summary: The risk for colon cancer is associated with nutrition, especially high fat and low calcium diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation.

Overall design: C57BL/6 mice received a Westernized high fat and low calcium diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. RNA was isolated from colon scrapings and subjected to gene expression profiling (n=7 control mice and n=9 heme-fed mice).

Background corr dist: KL-Divergence = 0.1483, L1-Distance = 0.0281, L2-Distance = 0.0012, Normal std = 0.3797

1.051 Kernel fit Pairwise Correlations Normal fit

Density 0.525

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

colon_control_repl1colon_heme_repl1colon_control_repl2 (0.0852558)colon_heme_repl2 (0.044111)colon_heme_repl3 (0.192407)colon_heme_repl4 (0.0398352)colon_control_repl3 (0.038726)colon_heme_repl5 (0.0484133)colon_control_repl4 (0.0459614)colon_heme_repl6 (0.0591645)colon_control_repl5 (0.0667768)colon_heme_repl7 (0.0225043)colon_control_repl6 (0.0693369)colon_heme_repl8 (0.0442442)colon_control_repl7 (0.0539833)colon_heme_repl9 (0.0565875) (0.0640045) (0.0686886)[ min ] [ medium ] [ max ] CEM 1 Col6a2 30.9 96.5 564.4 P ( S | Z, I ) = 1.00 Col6a1 99.2 313.9 2023.3 Mean Corr = 0.94787 Col6a3 23.5 67.4 699.0 Bgn 42.0 134.5 1259.7 Sspn 7.7 9.9 23.0 Crispld2 16.2 21.4 113.3 Col1a2 12.7 41.7 389.1 Col5a2 19.7 68.8 1196.0 Col1a1 36.5 92.0 709.0 Col5a1 16.3 28.3 190.7 Col3a1 18.0 57.6 794.4 CEM 1 + Sparc 97.3 438.4 2794.7 Top 10 Genes Pcolce 37.0 110.7 594.2 Mmp2 18.6 25.2 181.2 Fstl1 27.1 68.9 691.8 Ccdc80 17.0 24.1 174.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip 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,(0.080162) 1 type (0.0672059) sample,mice, replica brainVastusmice, replica wild biological tissue wild2biological muscletypeLateralis,(0.0751819) 2 type (0.0680308) sample,mice, replica brainVastusmice, replica mutant biological tissue mutant3biological muscleLateralis,(0.0621264) 3 mice, (0.0605737) sample, mice,replica brainVastus biological replica mutant biological tissue mutant4 Lateralis,(0.0540479) 4 mice, (0.0757828) replicasample, mice, replica biological mutant 1biological mutant(0.0793036) 1 (0.0751236) mice, replica mice, replica[ biological min 2biological (0.0885004) 2 (0.0801598) replica] replica 3 (0.0603881) 3 (0.0734132)[ medium ] [ max ] CEM 1 Col6a2 160.8 1053.5 2292.4 P ( S | Z, I ) = 1.00 Col6a1 260.7 1324.2 2203.4 Mean Corr = 0.94726 Col6a3 162.6 1547.1 3004.0 Bgn 303.6 1826.6 2614.6 Sspn 239.9 2621.7 3262.0 Crispld2 86.6 486.1 625.6 Col1a2 69.5 908.2 3001.7 Col5a2 80.2 738.0 1741.0 Col1a1 113.7 923.6 3575.2 Col5a1 183.6 658.5 1089.3 Col3a1 86.6 385.6 1265.7 CEM 1 + Sparc 4879.9 7398.3 12248.5 Top 10 Genes Pcolce 158.1 1326.1 1788.0 Mmp2 142.9 1270.6 2084.5 Fstl1 613.9 1672.3 3042.2 Ccdc80 337.2 675.1 2929.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE54349" 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=GSE54349 Status: Public on Jan 24 2014 Title: Expression data from colon and livers of mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARs role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research.

Here we describe our unprecedented approach in proposing parsley (PAR) as a nutraceutical intervention in inflammatory bowel disease (IBD) using a mouse model of dextran sodium sulphate (DSS)-induced colitis, following a multi-integrated-omics analysis. PAR supplementation (n=7) significantly improved colon shortening and increased the disease activity index compared to the DSS group (n=7). The colonic transcriptome revealed the down-regulation of inflammatory cytokines, and the hepatic transcriptome and metabolome revealed the up-regulation of fatty acid synthesis genes, thereby improving body weight loss. Down-regulated cancer markers were observed in the hepatic transcriptome and proteome. A global plasma metabolite analysis indicated shifts in the citric cycle and urea cycle, implicating improved impaired glycolysis and oxidative stress. Our integration of three omics analyses highlighted the involvement of the methionine-recycling pathway and PARs role in decreasing the risk of IBD. This pioneering use of multi-integrated-omics in the evaluation of nutrients effects on physiology is expected to be widely useful and informative, shaping the future of nutritional research.

Overall design: Total hepatic and colonic RNA from each respective group were pooled (n=7). The microarray analysis was carried as out as described by Jia et al. 8 Mouse Genome 430 2.0 Array GeneChips (Affymetrix, Santa Clara, CA) containing over 30,000 gene probe sets were used for genome-wide expression profiling.

Background corr dist: KL-Divergence = 0.0145, L1-Distance = 0.0248, L2-Distance = 0.0008, Normal std = 0.8186

0.487 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

CON ColonDSS (0.172064)ColonDSSPAR (0.189989)CON Colon LiverDSS (0.139361) (0.137686) LiverDSSPAR (0.194252) Liver (0.166648) [ min ] [ medium ] [ max ] CEM 1 Col6a2 16.7 996.6 2061.0 P ( S | Z, I ) = 1.00 Col6a1 101.8 968.9 1381.0 Mean Corr = 0.94507 Col6a3 183.7 1406.6 2463.4 Bgn 595.6 1307.0 2626.3 Sspn 82.2 520.1 624.3 Crispld2 21.2 504.9 1182.4 Col1a2 57.8 845.9 1538.0 Col5a2 104.0 1026.2 2650.1 Col1a1 11.1 78.6 182.6 Col5a1 121.7 462.7 1146.1 Col3a1 129.0 970.5 1843.0 CEM 1 + Sparc 1326.7 2654.9 5956.9 Top 10 Genes Pcolce 534.9 1099.0 1826.8 Mmp2 114.0 448.3 1147.2 Fstl1 119.3 1129.2 2256.6 Ccdc80 572.1 718.2 1278.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE40156" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 42 -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=GSE40156 Status: Public on Oct 30 2013 Title: Transcript atlases reveal that artery tertiary lymphoid organs but not secondary lymphoid organs control key steps of atherosclerosis T cell immunity in aged apoe-/- mice. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Tertiary lymphoid organs (TLOs) emerge in response to nonresolving inflammation but their roles in adaptive immunity remain unknown. Here, we explored artery TLOs (ATLOs) to delineate atherosclerosis T cell responses in apoe-/- mice during aging. Though the T cell repertoire showed systemic age-associated contractions in size and modifications in subtype composition and activation, wt and apoe-/- mice were equally affected. In contrast, ATLOs - but not wt aortae, apoe-/- aorta segments without ATLOs or atherosclerotic plaques - promoted T cell recruitment, altered characteristics of T cell motility, primed and imprinted T cells in situ, generated CD4+/FoxP3-, CD4+/FoxP3+, CD8+/FoxP3- effector and central memory cells, and converted naïve CD4+/FoxP3- T cells into induced Treg cells. ATLOs also showed substantially increased antigen presentation capability by conventional dendritic cells (DCs) and monocyte-derived DCs but not by plasmacytoid DCs. Thus, the senescent immune system specifically employs ATLOs to control dichotomic atherosclerosis T cell immune responses. We assembled transcriptome maps of wt and apoe-/- aortae and aorta-draining RLNs and identified ATLOs as major sites of atherosclerosis-specific T cell responses during aging: Transcriptome atlases of wt and apoe-/- abdominal aortae and associated draining RLNs were constructed from laser capture microdissection (LCM)-based whole genome mRNA expression microarrays yielding 6 maps: wt adventitia (tissue-1); wt RLN (tissue-2); apoe-/- ATLOs (tissue-3); apoe-/- RLN (tissue-4); apoe-/- adventitia without adjacent plaques (tissue-5), and plaques (tissue-6). Several two-tissue comparisons within the transcriptome atlases are noteworthy: Unexpectedly, transcriptomes of wt and apoe-/- RLNs were virtually identical; additonal data revealed that transcriptomes of RLNs were strikingly similar to those of inguinal LNs which do not drain the aorta adventitia (as shown of India ink injection experiments of surgically exposed aortae); in sharp contrast, wt adventitia versus ATLOs revealed 1405 differentially expressed transcripts many of which encoded members of GO terms immune response and inflammatory response; the ATLO-plaque comparison also showed > 1000 differentially expressed transcripts; however, wt adventitia versus apoe-/- adventitia without plaque showed few genes (< 5 % of differentially expressed transcripts of the wt adventitia-ATLO comparison). Thus, the aorta transcriptome atlases support the conclusion that neither aorta-draining apoe-/- RLNs nor ILNs participate in atherosclerosis-specific T cell responses. In addition, they demonstrate that T cell responses in the diseased aorta are highly territorialized. Finally, these data show that the immune responses carried out in ATLOs differ significantly from those carried out in plaques. We next identified three major clusters within the transcriptome atlases through ANOVA analyses and application of strict filters: An adventitia cluster, a plaque/ATLO cluster, and a LN/plaque cluster. The total number of differentially expressed genes in each cluster were examined for GO terms immune response, inflammatory response, T cell activation, positive regulation of T cell response, and T cell proliferation. Within the adventitia cluster, similarities of transcriptomes of wt adventitia and apoe-/- adventitia without associated plaque versus ATLOs indicate that a robust number of immune response-regulating genes are selectively expressed in ATLOs which are located within a distance of few ´m of the adventitia without associated plaques indicating a very high degree of territoriality of the atherosclerosis T cell response. Furthermore, unlike the total number of differentially regulated transcripts, the majority of transcripts among GO terms immune response and inflammatory response, was up-regulated. Inspection of the plaque/ATLO cluster provided further information: The majority of immune response regulating genes where expressed at a higher level in ATLOs when compared to plaques though plaques also contained a significant number of immune response regulating genes; the reverse is true for genes regulating inflammation. Finally, the lymph node cluster revealed that though the majority of immune response regulating genes resides in both wt and apoe-/- RLNs (with little differences between them) ATLOs express a selected set of immune response regulating genes at a higher level when compared to LNs. In addition, the inflammatory component of ATLOs when compared to LNs is documented by the finding that many more genes regulating inflammation reside in ATLOs even when compared to those of plaques.

Key words:

T cell response in atherosclerosis; Laser capture microdissection; transcriptome atlas of atherosclerosis.

Citations:

Gräbner R. et al. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J Exp Med 2009 Jan 16;206(1):233-48. PMID: 19139167;

Moos M. et al. The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2386-91. Epub 2005 Sep 22. PMID: 16179593;

Beer M. et al. Laser-capture microdissection of hyperlipidemic/ApoE-/- mouse aorta atherosclerosis. Methods Mol Biol. 2011;755:417-28. PMID: 21761324;

Weih F. et al. Control of Dichotomic Innate and Adaptive Immune Responses by Artery Tertiary Lymphoid Organs in Atherosclerosis. Front Physiol. 2012;3:226. Epub 2012 Jul 6. PMID: 22783198.

Overall design: Wild-type and apoE-deficient mice on the C57BL/6J genetic background were maintained on a standard mouse chow. Total aortae were removed at the age of 6 (n=3), 32 (n=3), or 78 (n=3) w and microarrays were prepared from total RNA extracts or extracts of atherosclerotic lesions and adventitiae obtained by the use of a laser dissection microscope. In addition, aorta associated LNs or distant LNs were prepared from both mouse genotypes.

Background corr dist: KL-Divergence = 0.1004, L1-Distance = 0.0740, L2-Distance = 0.0098, Normal std = 0.4788

0.955 Kernel fit Pairwise Correlations Normal fit

Density 0.478

0.000 CEM 1

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

Pre-normalization Quantiles

wt-Aorta-32-weeks-1wt-Aorta-32-weeks-3apoE-Aorta-32-weeks-1 (0.0225862)apoE-Aorta-32-weeks-2 (0.0263179)apoE-Aorta-32-weeks-3wt-Aorta-32-weeks-2 (0.0243905)wt-Aorta-6-weeks-1 (0.0250586)wt-Aorta-6-weeks-2 (0.0228647) (0.0262452)wt-Aorta-6-weeks-3 (0.0294277)apoE-Aorta-6-weeks-1 (0.034658)apoE-Aorta-6-weeks-2 (0.0247405)apoE-Aorta-6-weeks-3 wt-Aorta-78-weeks-1(0.0273444) wt-Aorta-78-weeks-2(0.0312313) wt-Aorta-78-weeks-3(0.0194549) (0.027006)apoE-Aorta-78-weeks-1 (0.0327821)apoE-Aorta-78-weeks-2 (0.0321341)apoE-Aorta-78-weeks-3apoE-Spleen-32-weeks-1 (0.0290348)apoE-Spleen-32-weeks-2 (0.0253268)apoE-Spleen-32-weeks-3 (0.0300927)apoE-Spleen-78-weeks-1 (0.0261377)apoE-Spleen-78-weeks-2 (0.0244506)apoE-Spleen-78-weeks-3 (0.0326069)wt-Spleen-32-weeks-1 (0.017877)wt-Spleen-32-weeks-2 (0.016237)wt-Spleen-32-weeks-3 (0.0144699) wt-Spleen-78-weeks-1(0.0158703) wt-Spleen-78-weeks-2(0.0190169) wt-Spleen-78-weeks-3(0.0245586) apoE-Blood-32-weeks-1(0.015801) apoE-Blood-32-weeks-2(0.0181969) apoE-Blood-32-weeks-3(0.0182626)apoE-Blood-78-weeks-1 (0.0190521)apoE-Blood-78-weeks-2 (0.0166316)apoE-Blood-78-weeks-3 (0.0199378)wt-Blood-32-weeks-1 (0.0221786)wt-Blood-32-weeks-2 (0.0212732)wt-Blood-32-weeks-3 (0.0283793) (0.0288048)wt-Blood-78-weeks-1 (0.0220129)wt-Blood-78-weeks-2 (0.0220382)wt-Blood-78-weeks-3 (0.0217645) (0.0214371) (0.0223081)[ min ] [ medium ] [ max ] CEM 1 Col6a2 198.8 957.4 13811.6 P ( S | Z, I ) = 1.00 Col6a1 18.2 838.9 10394.3 Mean Corr = 0.94304 Col6a3 148.7 744.5 9636.4 Bgn 44.0 6001.5 22615.3 Sspn 123.5 682.6 4705.7 Crispld2 79.5 586.8 4670.3 Col1a2 6.3 885.7 18183.8 Col5a2 14.1 423.2 11929.7 Col1a1 2.8 674.1 15097.3 Col5a1 53.7 651.7 7331.7 Col3a1 31.2 215.2 9954.1 CEM 1 + Sparc 15.8 4191.3 23368.3 Top 10 Genes Pcolce 5.5 2769.2 10681.9 Mmp2 70.1 602.8 8061.1 Fstl1 2.3 790.5 13140.0 Ccdc80 119.1 791.8 8145.7

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE44101" 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=GSE44101 Status: Public on Feb 08 2013 Title: Expression data from Spdef +/+ and Spdef -/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef -/- mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef -/- mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye.

Microarray analysis of conjunctival epithelium in Spdef -/- mice identified 43 signficantly upregulated genes and 110 signficantly downregulated genes in the conjunctival epithelium of Spdef -/- mice compared to that of Spdef +/+ control mice (3 fold change, p<0.01). Downregulated genes of particular interested included goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Upregulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and pro-inflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are upregulated in dry eye. Interestingly, four Wnt pathway genes were downregulated.

Overall design: Conjunctival epithelium of Spdef +/+ and Spdef -/- mice was collected by laser capture microdissection for RNA extraction and hybridization on Affymetrix microarrays to determine if gene expression patterns in the conjunctival epithelium of Spdef -/- mice is altered compared to that of Spdef +/+ mice.

Background corr dist: KL-Divergence = 0.0238, L1-Distance = 0.0211, L2-Distance = 0.0004, Normal std = 0.7228

0.565 Kernel fit Pairwise Correlations Normal fit

Density 0.283

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

Spdef +/+Spdef mice, +/+Spdef biological mice, +/+Spdef biological mice, rep1 -/-Spdef biologicalmice,(0.12103) rep2 -/- Spdefbiological mice,(0.139694) rep3 -/- biological mice,(0.232825) rep1 biological(0.177763) rep2 (0.0891014) rep3 [(0.239586) min ] [ medium ] [ max ] CEM 1 Col6a2 2086.2 4121.1 6604.9 P ( S | Z, I ) = 1.00 Col6a1 1659.2 3020.5 5462.0 Mean Corr = 0.94104 Col6a3 581.1 1001.6 1590.5 Bgn 5415.9 6304.9 8233.8 Sspn 62.6 165.6 328.5 Crispld2 213.8 844.4 1264.7 Col1a2 1756.1 3429.6 8044.3 Col5a2 888.1 970.4 1890.2 Col1a1 2043.8 4408.1 8867.9 Col5a1 520.0 872.1 2040.9 Col3a1 920.1 1264.0 3253.2 CEM 1 + Sparc 3568.5 5251.9 11391.9 Top 10 Genes Pcolce 4596.0 5858.6 6237.9 Mmp2 928.9 2244.7 4089.2 Fstl1 860.5 1683.4 4199.9 Ccdc80 228.4 416.3 1326.7

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip 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(0.0248599) 0-replicate tissue-time2 Joint(0.0216501) 2 weeks-sham-replicate tissue-time3 Joint(0.0210861) 2 weeks-sham-replicate tissue-timeJoint 2 weeks-sham-replicate tissue-timeJoint 4 weeks-sham-replicate1 tissue-time(0.0202571)Joint 4 weeks-sham-replicate2 tissue-time(0.034611)Joint 4 weeks-sham-replicate3 tissue-time(0.0632286)Joint 8 weeks-sham-replicate1 tissue-time(0.0134818)Joint 8 weeks-sham-replicate2 tissue-time(0.0360814)Joint 8 weeks-sham-replicate3 tissue-time(0.0226299)Joint 16 1 weeks-sham-replicate tissue-time(0.0297363)Joint 16 2 weeks-sham-replicate tissue-time(0.0282157)Joint 16 3 weeks-sham-replicate tissue-time(0.0539101)Joint 2 weeks-DMM-replicate 1tissue-time (0.0463057)Joint 2 weeks-DMM-replicate 2tissue-time (0.0281581)Joint 4 weeks-DMM-replicate 3tissue-time (0.0415456)Joint 4 2weeks-DMM-replicate (0.0907178)tissue-timeJoint 4 3weeks-DMM-replicate (0.122789)tissue-timeJoint 8 1weeks-DMM-replicate (0.0132205)tissue-timeJoint 8 2weeks-DMM-replicate (0.0645937)tissue-timeJoint 8 3weeks-DMM-replicate (0.0519078)tissue-timeJoint 16 1 weeks-DMM-replicate(0.031185)tissue-time 16 2 weeks-DMM-replicate(0.0313904) 16 3 weeks-DMM-replicate(0.0175672) 1 (0.031605)[ min 2 (0.0227438) ]3 (0.0365224)[ medium ] [ max ] CEM 1 Col6a2 1194.1 3093.4 14801.9 P ( S | Z, I ) = 1.00 Col6a1 630.9 1875.0 9257.6 Mean Corr = 0.94038 Col6a3 2375.6 5129.7 19200.0 Bgn 6310.1 9526.6 21149.2 Sspn 348.7 624.4 1116.0 Crispld2 1027.4 1423.5 3223.7 Col1a2 17318.0 26509.6 40693.7 Col5a2 3929.5 9431.7 24625.2 Col1a1 6284.4 12777.7 21006.8 Col5a1 1260.9 2214.6 8312.8 Col3a1 753.6 3373.9 18642.9 CEM 1 + Sparc 19991.8 31951.3 47329.9 Top 10 Genes Pcolce 1859.1 4106.3 12537.8 Mmp2 698.0 2238.2 11647.6 Fstl1 2195.1 3584.7 12810.3 Ccdc80 2549.3 5094.4 10400.0

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE42601" 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=GSE42601 Status: Public on Jun 01 2013 Title: Expression data from wild-type and Dazap1 mutant mouse testes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23965306 Summary & Design: Summary: Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous RNA-binding protein that is highly expressed in the testis. It is a component of the hnRNP particles and shuttles between the nucleus and the cytoplasm. Mice expressing the DAZAP1-Fn mutant protein manifest both growth retardation and spermatogenic arrest before meiosis I. To elucidate the biological function(s) of DAZAP1 and to search for its natural RNA substrates, we compared the expression profiles of wild-type and Dazap1 mutant testes by cDNA microarrays.

Overall design: We used wild-type and Dazap1 mutant mouse testes. Each genotype has three replicates. 6 total samples were analyzed.

Background corr dist: KL-Divergence = 0.0070, L1-Distance = 0.0271, L2-Distance = 0.0008, Normal std = 0.9770

0.430 Kernel fit Pairwise Correlations Normal fit

Density 0.215

0.000 CEM 1

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

Pre-normalization Quantiles

Wild-typeMutant testes Wild-typetestes at P21, atMutant P21,biological testes biological Wild-typetestes at P21,rep1 atMutant P21,biological rep1(0.155052)testes biological(0.204814)testes at P21,rep2 at P21,biologicalrep2(0.130034) biological(0.171645) rep3[ rep3(0.183695)min (0.154761) ] [ medium ] [ max ] CEM 1 Col6a2 1530.9 3548.9 3786.6 P ( S | Z, I ) = 1.00 Col6a1 1593.3 3597.3 4126.9 Mean Corr = 0.93820 Col6a3 856.3 2011.6 2233.2 Bgn 1658.2 2733.8 4355.8 Sspn 306.3 712.7 820.2 Crispld2 484.9 752.6 885.7 Col1a2 3017.8 8076.4 9276.6 Col5a2 258.0 1226.5 1317.1 Col1a1 2061.5 4778.0 5799.5 Col5a1 404.7 748.7 791.1 Col3a1 639.8 2187.0 2371.2 CEM 1 + Sparc 12945.5 19866.3 21326.7 Top 10 Genes Pcolce 2981.4 3428.7 4833.5 Mmp2 238.7 594.7 743.4 Fstl1 1132.5 2608.7 2766.1 Ccdc80 190.2 578.8 662.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE26299" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 108 -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=GSE26299

Background corr dist: KL-Divergence = 0.0440, L1-Distance = 0.0244, L2-Distance = 0.0009, Normal std = 0.5775 GEO Series "GSE5671" 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=GSE5671 Status: Public on Aug 30 2007 Title: Cardiac differentiation of embryonic stem cells recapitulates embryonic cardiac development. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18246200 Summary & Design: Summary: Mouse embryonic stem cells can differentiate in vitro into spontaneously contracting cardiomyocytes. The main objective of this study was to investigate cardiogenesis in cultures of differentiating embryonic stem cells (ESCs) and to determine how closely it mimics in vivo cardiac development. We identified and isolated a population of cardiac progenitor cells (CPCs) through the use of a reporter DNA construct that allowed the expression of a selectable marker under the control of the Nkx2.5 enhancer. We proceeded to characterize these CPCs by examining their capacity to differentiate into cardiomyocytes and to proliferate. We then performed a large-scale temporal microarray expression analysis in order to identify genes that are uniquely upregulated or downregulated in the CPC population. We determined that the transcriptional profile of the mESC derived CPCs was consistent with pathways known to be active during embryonic cardiac development. We conclude that in vitro differentiation of mESCs recapitulates the early steps of mouse cardiac development.

Keywords: embryonic stem cell, differentiation, cardiac progenitor, cardiogenesis

Overall design: The Spotfire DecisionSite software package was used for the identification of uniquely upregulated or downregulated (at least 1.5 times increase or decrease in the expression value) probe sets in the CPC population when compared to the rest of the cells in the differentiating EBs. Probe sets that were considered unique for the CPC population were found to be commonly upregulated or downregulated during all four days of analysis. Probe sets that exhibited an increasing or decreasing pattern of expression with at least 1.5 times increase or decrease in the expression values of day 5 CPCs and day 8 CPCs were also reported. Probe sets of the CPC population that exhibited upregulation or downregulation by at least 1.5 times when compared to the mESC derived cardiomyocytes were also reported. The final analysis included probe sets that exhibited a different temporal pattern of expression in the CPC population when compared to the rest of the cells along the four days of differentiation. Specifically in order to identify these probe sets gene expression curve over time was modeled flexibly

Background corr dist: KL-Divergence = 0.1448, L1-Distance = 0.0419, L2-Distance = 0.0032, Normal std = 0.3990

1.040 Kernel fit Pairwise Correlations Normal fit

Density 0.520

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

Day 5 GFPDay Negative 5 GFPDay Positive 6 Batch GFPDay Negative 61Batch GFP(0.037907)Day Positive 17 Batch (0.0294526)GFPDay Positive 71Batch GFP(0.0337859)Day Negative 1 8Batch (0.0265236)GFPDay Positive 18 Batch (0.0384572)GFPDay Negative 51Batch GFP(0.0386342)Day Negative 15 Batch (0.054333)GFPDay Positive 61 Batch GFP(0.0700082)Day Negative 62Batch GFP(0.0560501)Day Positive 27 Batch (0.0674628)GFPDay Negative 72Batch GFP(0.0456314)Day Positive 28 Batch (0.065546)GFPDay Negative 82Batch GFP(0.0359582)Mouse Positive2 Batch(0.0297455) embryonicMouse 2Batch (0.0424996) embryonic stem2 (0.0549697) cell stem derived cell derived cardiomyocytes[ min cardiomyocytes ] 1 (0.129161) 2 (0.143874)[ medium ] [ max ] CEM 1 Col6a2 26.2 204.0 2643.7 P ( S | Z, I ) = 1.00 Col6a1 100.6 202.5 2769.5 Mean Corr = 0.93286 Col6a3 53.0 143.5 794.1 Bgn 128.8 237.0 11170.6 Sspn 5.4 84.5 2514.3 Crispld2 7.0 147.4 1380.5 Col1a2 13.1 621.1 7733.4 Col5a2 105.0 1196.0 22634.7 Col1a1 6.7 107.7 2474.0 Col5a1 308.5 1214.1 10378.8 Col3a1 19.4 353.7 5371.4 CEM 1 + Sparc 1468.2 4872.5 34693.5 Top 10 Genes Pcolce 110.3 377.9 14762.2 Mmp2 825.0 1795.3 10851.7 Fstl1 2065.4 5719.5 24230.9 Ccdc80 132.8 933.5 10552.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE7694" 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=GSE7694 Status: Public on Jun 11 2007 Title: Cannabinoid receptor double knockout mice (Cnr1 -/- /Cnr2 -/-) in CHS model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17556587 Summary & Design: Summary: We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention.

Keywords: Strain (Wt versus Ko) and disease state (DNFB treated versus control).

Overall design: Three wildtype mice (Wt) and three Cnr1-/-/Cnr2-/- (Ko) mice were used. Contact hypersensitivity was determined always at the right ears, which therefore were treated with DNFB (Tr). Left ears of mice were kept untreated and served as control ears (C). A total of 12 hybridizations were performed (2 strains x 2 treatments X 3 biological replicates) in this experiment.

Background corr dist: KL-Divergence = 0.0647, L1-Distance = 0.0516, L2-Distance = 0.0039, Normal std = 0.5463

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

C57BL/6JC57BL/6J femaleC57BL/6J numberfemaleC57BL/6J numberfemale 1, untreatedC57BL/6J numberfemale 2, untreatedC57BL/6J control numberfemale 3, untreatedCnr1-/-/Cnr2-/- controlear numberfemale 1, (#1_Wt-C-3) DNFB-treatedCnr1-/-/Cnr2-/- controlear number 2, (#2_Wt-C-4) DNFB-treated femaleCnr1-/-/Cnr2-/- ear (0.091371) 3, allergic(#3_Wt-C-7) DNFB-treated numberfemaleCnr1-/-/Cnr2-/- (0.0500587) allergicear numberfemale Cnr1-/-/Cnr2-/-1, (#4_Wt-Tr-3) (0.0807711)untreated allergicear numberfemale Cnr1-/-/Cnr2-/-2, (#5_Wt-Tr-4) untreated earcontrol number(0.0966495)female 3, (#6_Wt-Tr-7) untreated controlear number(0.0988382)female 1, (#7_Ko-C-4) DNFB-treated controlear number(0.0600781) 2, (#8_Ko-C-5) DNFB-treated ear (0.0850806) [3, allergic(#9_Ko-C-7) DNFB-treatedmin (0.105277) allergicear ] (#10_Ko-Tr-4) (0.0856948) allergicear (#11_Ko-Tr-5) ear[ (0.0643196)medium (#12_Ko-Tr-7) (0.0992108) (0.0826508) ] [ max ] CEM 1 Col6a2 3625.9 6215.7 9858.6 P ( S | Z, I ) = 1.00 Col6a1 3626.4 7967.9 11379.7 Mean Corr = 0.93074 Col6a3 4560.6 6770.4 9690.8 Bgn 7339.7 12412.7 15656.7 Sspn 663.2 1452.8 1938.4 Crispld2 1057.6 1460.7 1954.3 Col1a2 10383.8 13353.8 20280.2 Col5a2 4575.4 6732.1 7741.8 Col1a1 4970.1 7412.1 12189.9 Col5a1 1076.8 1853.7 2581.0 Col3a1 2438.4 4399.4 5830.8 CEM 1 + Sparc 14603.3 22458.5 33219.3 Top 10 Genes Pcolce 3247.5 4410.1 5489.9 Mmp2 3486.0 6868.6 8823.9 Fstl1 5442.2 7076.2 7991.9 Ccdc80 3485.7 8045.7 10559.7

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE45820" 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=GSE45820 Status: Public on May 19 2014 Title: Expression data from murine cardiac fibroblasts and endothelial cells following Transverse Aortic Constriction Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Accumulation of activated cardiac fibroblasts plays a key role in heart failure progression. These cells deposit excessive extracellular matrix that leads to mechanical stiffness, myocyte uncoupling and ischemia. To investigate whether two developmentally distinct cardiac fibroblast populations exhibit distinct expression profiles in response to cardiac injury, and therefore might necessitate distinct therapeutic targeting, we performed microarray analysis on FACS sorted cells. Tie2cre lineage traced CFs, non Tie2cre lineage traced cardiac fibroblasts and endothelial cells were isolated from left ventricle of SHAM operated and banded hearts at the onset of fibrosis, one week after surgery.

We used microarrays to detail the global programme of gene expression in cardiac fibroblasts and endothelium following pressure overload. Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 TAC operated adult male Black Swiss mice.

Overall design: Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 Transaortic Constriction (TAC) operated adult male Black Swiss mice for RNA extraction and Affymetrix microarray analysis. Hypertrophy in TAC animals, an lack of hypertrophy in SHAM operated animals, was evaluated by hemodynamic measurements before surgery and one week after surgery. Cells were isolated one week after surgery.

Background corr dist: KL-Divergence = 0.0132, L1-Distance = 0.0279, L2-Distance = 0.0011, Normal std = 0.8360

0.477 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

Tie2cre Tie2crelineage Tie2cre lineagetraced Tie2cre fibroblastnon-lineagetraced Endothelialfibroblastnon-lineage SHAM, tracedEndothelial BiologicalTAC, cells fibroblasttraced Biological SHAM, cellsfibroblast Replicate SHAM, BiologicalTAC, Replicate BiologicalTAC, 1 (0.110067) ReplicateBiological 1[ (0.142644) minReplicate 1 Replicate (0.355399) ] 1 (0.0989505)(0.163256) 1 (0.129684)[ medium ] [ max ] CEM 1 Col6a2 401.8 14280.9 14875.3 P ( S | Z, I ) = 1.00 Col6a1 179.8 14005.5 15333.3 Mean Corr = 0.92925 Col6a3 50.6 5981.0 6978.1 Bgn 1492.3 14368.3 15164.1 Sspn 79.8 1761.6 2067.0 Crispld2 151.7 5333.3 8863.7 Col1a2 93.7 9954.4 16321.0 Col5a2 137.9 9118.6 17091.8 Col1a1 225.9 15921.7 18343.4 Col5a1 216.7 9539.3 11298.4 Col3a1 26.2 5554.5 8541.4 CEM 1 + Sparc 18477.2 21264.4 22628.7 Top 10 Genes Pcolce 1172.9 10432.3 12436.0 Mmp2 35.3 8259.1 8819.2 Fstl1 303.1 8665.4 13872.3 Ccdc80 277.1 8637.4 9190.3

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE23845" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 15 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23845 Status: Public on Aug 28 2010 Title: Time course for bladder UCC development in UPII-SV40Tag mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20501863 Summary & Design: Summary: We have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive UCC, respectively

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

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

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

1.002 Kernel fit Pairwise Correlations Normal fit

Density 0.501

0.000 CEM 1

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

Pre-normalization Quantiles

3wk Wild3wk type Wild biological3wk type UPII-SV40Tag biological3wk rep UPII-SV40Tag #16wk (0.14487) rep biological Wild #26wk (0.0444019)type biological UPII-SV40Tag repbiological6wk #1 UPII-SV40Tag (0.0423941) rep20wk rep #2 biological Wild(0.0434645)#120wk (0.0771779) type biological Wild rep20wk biological type#1 UPII-SV40Tag(0.0338841) rep20wk biological #2rep UPII-SV40Tag(0.0544267) 30wk#1 (0.0637916) rep biological Wild 30wk#2 (0.0434055)type biological Wild30wk repbiological type #1 UPII-SV40Tag (0.078851)30wk repbiological rep #2 UPII-SV40Tag (0.0402685)#1 (0.0769725) rep biological #2 (0.0792512) biological rep #1 (0.087389) [rep min #2 (0.0894517) ] [ medium ] [ max ] CEM 1 Col6a2 32.4 120.1 3250.8 P ( S | Z, I ) = 1.00 Col6a1 67.5 208.6 3416.5 Mean Corr = 0.92377 Col6a3 165.6 282.4 2770.6 Bgn 118.1 237.0 2676.3 Sspn 3.9 52.9 288.5 Crispld2 2.8 82.8 599.4 Col1a2 3.8 136.3 7154.0 Col5a2 39.5 104.9 2277.9 Col1a1 3.4 204.6 7176.0 Col5a1 51.4 114.9 982.1 Col3a1 18.0 80.2 2225.8 CEM 1 + Sparc 138.5 992.2 8055.6 Top 10 Genes Pcolce 113.4 378.4 2016.0 Mmp2 21.9 134.4 2689.0 Fstl1 39.8 175.2 2486.0 Ccdc80 121.3 189.3 1077.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE15267" 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=GSE15267 Status: Public on Mar 18 2009 Title: Expression data of induced pluripotent stem cell Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20595395 Summary & Design: Summary: We present a robust serum-free system for the rapid and efficient reprogramming of mouse somatic cells by Oct4, Sox2 and Klf4. The elimination of fetal bovine serum and oncogene c-Myc allowed reprogramming cells to be detected as early as Day 2 and reached greater than 10% of the population at Day 7 post retroviral transduction. The resulting iPS colonies were isolated with high efficiency to establish pluripotent cell lines. Based on this method, we further developed iPS-SF1 as a dedicated reprogramming medium for chemical screening and mechanistic investigations.

Comparasion of iPS cell lines derived from serum-free culture condition, MEF cells cultured in serum and serum-free condition and ES cell lines was shown.

Overall design: Selected induced pluripotent stem cell lines and its original mouse embroynic fibroblast were comparaed to defined mouse embroynic stem cell lines: R1 and CGR8.

Background corr dist: KL-Divergence = 0.0267, L1-Distance = 0.0218, L2-Distance = 0.0006, Normal std = 0.7121

0.569 Kernel fit Pairwise Correlations Normal fit

Density 0.284

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

embryonicMEF stem culturedMEF cell cultured lineinembryonic serum-free CGR8 in4F-serumfree serum(0.0899855) stem medium4F-serumfree medium cell lineiPS(0.263262)3F-serumfree (0.22718) R1cell (0.11498)iPS line3F-serumfree cell S2C12 iPS line cell (0.0712111)S2C16 iPS line cell (0.0938699)S53C1 line (0.0670239)S53C5[ min(0.0724883) ] [ medium ] [ max ] CEM 1 Col6a2 246.7 379.4 18977.1 P ( S | Z, I ) = 1.00 Col6a1 51.2 171.6 12578.6 Mean Corr = 0.92291 Col6a3 67.6 276.8 17343.6 Bgn 88.5 1389.0 36168.3 Sspn 28.0 35.9 1436.1 Crispld2 92.4 139.9 456.0 Col1a2 44.7 440.1 30788.8 Col5a2 43.1 710.8 27533.2 Col1a1 91.2 720.2 44476.4 Col5a1 281.9 579.9 18842.8 Col3a1 18.5 30.1 12431.1 CEM 1 + Sparc 3880.1 5126.9 35172.3 Top 10 Genes Pcolce 1521.6 2151.3 18140.9 Mmp2 188.0 723.2 15249.2 Fstl1 1601.8 5797.5 37380.4 Ccdc80 49.4 478.5 13760.9

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE7810" 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=GSE7810 Status: Public on May 18 2007 Title: Comparative analysis of gene expression WT and Nrf2-/- mice Type II cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17895394 Summary & Design: Summary: We hypothesize that gene expression in the Type II cells of Nrf2+/+ and Nrf2-/- mice are divergent thus contributing the cell growth. More specifically, type II cells from Nrf2-/- mice have increased reactive oxygen species that cause the impaired cell growth. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Nrf2+/+ and Nrf2-/- cells.

Keywords: comparative expression profiling

Overall design: . This study utilizes microarray analysis to test these hypotheses. Three sets of type II cells were isolated from lungs from both Nrf2+/+ and Nrf2-/- mice and grown for 5 days. RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430 2.0 array). Statistically significant gene expression was determined as a minimum 6 counts of 9 pairwise comparisons, minimum 1.5-fold change, and p < 0.05. Further, Absolute | FC - FC SEM | >= 1.5.

Background corr dist: KL-Divergence = 0.0624, L1-Distance = 0.0171, L2-Distance = 0.0003, 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

MNR 1-2MNR WT 2-23 (0.0710082)MNR WT 5-24 (0.0719387)MNR KO 26-2 (0.108886)MNR KO 37-2 (0.0975685)MNR KO Treated8-2MNR KO Treated1-3 2 MNR(0.1494) WT 2-35 3 (0.102679) MNR(0.136822) KO 43-3 (0.112395) KO Treated 4 (0.149303)[ min ] [ medium ] [ max ] CEM 1 Col6a2 304.9 811.3 1430.1 P ( S | Z, I ) = 1.00 Col6a1 195.0 881.6 1363.3 Mean Corr = 0.92030 Col6a3 337.9 1100.5 2105.3 Bgn 5045.2 11019.6 16361.5 Sspn 100.1 276.6 387.5 Crispld2 45.7 765.9 1269.7 Col1a2 3205.4 13431.5 17355.3 Col5a2 4631.2 14687.7 21208.3 Col1a1 4420.7 13689.9 26560.9 Col5a1 1168.2 4253.4 5612.5 Col3a1 117.7 947.9 1434.8 CEM 1 + Sparc 8433.5 20237.3 31596.7 Top 10 Genes Pcolce 618.6 4577.9 5986.8 Mmp2 2445.2 3944.1 5663.6 Fstl1 2496.8 7956.8 11973.3 Ccdc80 4027.3 6780.9 8176.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE9013" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: Comparitive gene expression analysis

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

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

0.845 Kernel fit Pairwise Correlations Normal fit

Density 0.423

0.000 CEM 1

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

Pre-normalization Quantiles

CD45-negativeCD45-negative IntactSP cell jejunum, CD45-negativenSPfraction, cell CD45-negativebiological fraction,biological IntactSP biologicalrep1cell rep1 jejunum, CD45-negativenSPfraction, (0.0857387) (0.080631) cell rep1 CD45-negativebiological fraction,biological (0.0920612) IntactSP biologicalrep2cell rep2 jejunum, CD45-negativenSPfraction, (0.0608961) (0.119393) cell rep2 CD45-negativebiological fraction,biological (0.0791703) IntactSP biologicalrep3cell rep3 jejunum, nSPfraction, (0.0801437) (0.0451426) cell rep3 biological fraction,biological (0.122855) biologicalrep4 rep4[ (0.0763925) (0.0633075)min rep4 (0.0942683)] [ medium ] [ max ] CEM 1 Col6a2 73.4 1258.3 9591.3 P ( S | Z, I ) = 1.00 Col6a1 104.7 401.4 4954.9 Mean Corr = 0.91633 Col6a3 87.4 849.3 7271.8 Bgn 227.0 3150.4 9053.9 Sspn 15.0 206.8 564.5 Crispld2 54.4 293.4 2760.2 Col1a2 21.8 320.4 3154.2 Col5a2 72.3 443.0 5637.2 Col1a1 7.8 70.3 1367.3 Col5a1 98.8 460.4 3226.0 Col3a1 26.8 214.8 2249.0 CEM 1 + Sparc 334.9 603.3 7393.7 Top 10 Genes Pcolce 70.9 138.4 3347.0 Mmp2 223.0 2710.8 4424.2 Fstl1 200.5 353.7 6623.6 Ccdc80 39.3 123.0 3511.4

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE13302" 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=GSE13302 Status: Public on May 12 2009 Title: Gene expression profiling in the lung and liver of Perfluorooctane sulfonate (PFOS) exposed mouse fetuses Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19429403 Summary & Design: Summary: Most of the transcriptional changes induced by PFOS in the fetal mouse liver and lung were related to activation of PPARalpha. When compared to the transcript profiles induced by PFOA (Pubmed ID 17681415), few remarkable differences were found other than up-regulation of Cyp3a genes. Because PFOS and PFOA have been shown to differ in their mode of action in the murine neonate, these data suggest that changes related to PFOS-induced neonatal toxicity may not be evident in the fetal transcriptome at term.

Overall design: Thirty timed-pregnant CD-1 mice were orally dosed from gestation day 1-17 with either 0, 5, or 10 mg/kg/day PFOS in 0.5% Tween 20. At term, fetal lung and liver were collected, total RNA prepared, and samples pooled from three fetuses per litter. Five biological replicates consisting of individual litter samples were then evaluated for each treatment group using Affymetrix mouse 430_2 microarrays.

Background corr dist: KL-Divergence = 0.0214, L1-Distance = 0.0694, L2-Distance = 0.0077, Normal std = 0.8465

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

0mg/kg/day0mg/kg/day PFOS,0mg/kg/day lungPFOS,0mg/kg/day rep1 liverPFOS, (0.0378725)0mg/kg/day rep1 lungPFOS, (0.0400746)0mg/kg/day rep2 liverPFOS, (0.0444762)0mg/kg/day rep2 lungPFOS, (0.0314165)0mg/kg/day rep3 liverPFOS, (0.0278421)0mg/kg/day rep3 lungPFOS, (0.0481535)0mg/kg/day rep4 liverPFOS, (0.0490394)5mg/kg/day rep4 lungPFOS, (0.0331937)5mg/kg/day rep5 liverPFOS, (0.026574)5mg/kg/day rep5 lungPFOS, (0.0254454)5mg/kg/day rep1 liverPFOS, (0.0207119)5mg/kg/day rep1 lungPFOS, (0.0404075)5mg/kg/day rep2 liverPFOS, (0.0234759)5mg/kg/day rep2 lungPFOS, (0.0289083)5mg/kg/day rep3 liverPFOS, (0.0311062)5mg/kg/day rep3 lungPFOS, (0.0348305)5mg/kg/day rep4 liverPFOS, (0.0302829)10mg/kg/day rep4 lungPFOS, (0.0260343)10mg/kg/day rep5 liver PFOS, (0.0348314)10mg/kg/day rep5 lungPFOS, (0.0250673)10mg/kg/day rep1 liverPFOS, 10mg/kg/day(0.0283449) rep1 lungPFOS, 10mg/kg/day(0.0270257) rep2 liverPFOS, 10mg/kg/day(0.0215282) rep2 lungPFOS, 10mg/kg/day(0.0502096) rep3 liverPFOS, 10mg/kg/day(0.0271411) rep3 lungPFOS, 10mg/kg/day(0.0408038) rep4 liverPFOS, (0.0278673) rep4 lungPFOS, (0.0494168) rep5 liver (0.0315115) rep5 [(0.0364071) min ] [ medium ] [ max ] CEM 1 Col6a2 669.2 12110.4 16582.7 P ( S | Z, I ) = 1.00 Col6a1 462.2 9441.1 14723.0 Mean Corr = 0.91521 Col6a3 627.9 13466.2 19570.9 Bgn 1434.5 10963.3 12871.2 Sspn 27.4 117.5 395.3 Crispld2 236.4 340.6 529.9 Col1a2 763.7 7132.6 10893.6 Col5a2 1029.6 5184.7 6601.6 Col1a1 615.9 3291.3 11872.2 Col5a1 1413.8 2034.7 2607.3 Col3a1 311.0 2714.2 3992.6 CEM 1 + Sparc 3814.0 20584.1 26958.7 Top 10 Genes Pcolce 459.8 1651.9 2271.9 Mmp2 195.5 2360.1 4040.5 Fstl1 930.8 12680.3 16683.3 Ccdc80 1701.2 2591.6 3213.3

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE10556" 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=GSE10556 Status: Public on Nov 07 2008 Title: Comparision of expression profile between wild-type and Slc39a13 knockout chondrocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18985159 Summary & Design: Summary: In order to explore molecules whose expression is controlled by Slc39a13, we investigated gene expression profiling of primary chondrocyte isolated from wild-type and Slc39a13 knockout mice.

Keywords: knockout vs wild-type

Overall design: wild-type vs Slc39a13 knockout

Background corr dist: KL-Divergence = 0.0339, L1-Distance = 0.0199, L2-Distance = 0.0004, Normal std = 0.6472

0.620 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

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

Pre-normalization Quantiles

chondrocytechondrocyte wildchondrocyte type-rep1 wildchondrocyte type-rep2 (0.14461)wildchondrocyte type-rep3 (0.124294)Slc39a13chondrocyte (0.11167)Slc39a13 knockout-rep1 Slc39a13 knockout-rep2 knockout-rep3(0.311853) [(0.123063) min (0.184511) ] [ medium ] [ max ] CEM 1 Col6a2 7294.4 11498.2 12540.0 P ( S | Z, I ) = 1.00 Col6a1 7833.4 11439.7 12477.8 Mean Corr = 0.91466 Col6a3 5069.9 7041.7 7705.9 Bgn 19188.6 24373.3 31692.5 Sspn 1055.1 1313.9 1448.9 Crispld2 40.4 336.2 397.0 Col1a2 7858.9 14197.0 16041.7 Col5a2 22604.1 28902.4 32012.0 Col1a1 5984.6 8854.4 13718.6 Col5a1 4850.9 9241.9 10054.9 Col3a1 423.2 458.4 478.5 CEM 1 + Sparc 35437.0 44936.9 70079.4 Top 10 Genes Pcolce 14918.4 16478.7 21416.6 Mmp2 1893.6 2604.5 2990.8 Fstl1 11588.7 15875.7 17108.5 Ccdc80 13600.7 17432.6 19866.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE13874" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.482 Kernel fit Pairwise Correlations Normal fit

Density 0.241

0.000 CEM 1

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

Pre-normalization Quantiles

NTg, biologicalNTg, biologicalNTg, replicate biologicalNTg, replicate 1 (Affymetrix) biologicalCalcineurin replicate 2 (Affymetrix)Calcineurin replicate (0.0323132) 3 (Affymetrix)Tg,Calcineurin biological (0.0576648) 4 (Affymetrix)Tg,Calcineurin biological (0.0740472) replicate Tg,Differentiating biological (0.0405391) replicate Tg, 1 (Affymetrix)Differentiating biological replicate 2 P19CL6(Affymetrix)Differentiating replicate (0.0620027) 3 P19CL6(Affymetrix)Differentiating cells (0.0506878) 4at P19CL6(Affymetrix)Differentiating cellsday (0.0540721)6 at afterP19CL6Differentiating cellsday DMSO(0.0711648)6 at afterP19CL6 cellsday treatment, DMSO6 at afterP19CL6 cellsday treatment, DMSO10 at replicate aftercellsday treatment, 10 DMSOat replicate[ afterday 1min (Affymetrix) 10 treatment,DMSO replicate after 2 (Affymetrix)] treatment,DMSO (0.112934)replicate 3 (Affymetrix) treatment, (0.0781501)replicate [1 (Affymetrix)medium (0.0977585)replicate 2 (Affymetrix) (0.115466) 3 (Affymetrix) ] (0.0700822) (0.0831173)[ max ] CEM 1 Col6a2 84.8 1645.5 6615.1 P ( S | Z, I ) = 1.00 Col6a1 186.9 1894.9 6616.0 Mean Corr = 0.91435 Col6a3 114.6 930.2 3395.1 Bgn 34.7 5041.0 15766.1 Sspn 4.5 5601.4 8604.9 Crispld2 61.8 1363.0 3042.1 Col1a2 84.7 951.5 6342.2 Col5a2 688.4 3420.1 6495.4 Col1a1 95.2 948.0 8852.4 Col5a1 608.6 1932.7 6304.1 Col3a1 5.0 451.7 2611.9 CEM 1 + Sparc 4123.0 9673.3 21336.3 Top 10 Genes Pcolce 456.7 2203.4 6813.4 Mmp2 527.8 1596.2 3830.7 Fstl1 1197.3 3893.3 6908.0 Ccdc80 910.2 2832.5 7700.0

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE34618" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 7 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34618 Status: Public on May 02 2012 Title: Expression data from CD8+ Central memory T cells after different time periods of Concanavalin A in vitro activation. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22567129 Summary & Design: Summary: CD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling shown to result from inactivation of p56lck kinase. We identify a novel interacting partner for p56lck in nonlytic TIL, Protocadherin-18 (pcdh18), and show that pcdh18 is transcribed upon in vitro or in vivo activation of CD8+ central memory T cells (CD44+CD62LhiCD127+) coincident with conversion into effector memory cells (CD44+CD62LloCD127+). Expression of pcdh18 in primary CD8+ effector cells induces the phenotype of nonlytic TIL: defective; proximal TCR signaling, cytokine secretion, and cytolysis; and enhanced AICD. pcdh18 contains a motif (centered at Y505) shared with src kinases (QGQYQP) which is required for the inhibitory phenotype. Thus, pcdh18 is a novel marker of CD8+ effector memory T cells expressed upon cell activation that can function as a negative regulator by restricting the effector phase.

We used microarrays to detail the global programme of gene expression underlying CD8+ 'Central memory' T cells activation and identified distinct transcriptional pattern clusters.

Overall design: Ten spleens were pooled from 62 week old C57BL/6 male mice and enriched for CD8+ T cells by negative selection using a cocktail of biotinylated antibodies to deplete CD4, CD11c, CD11b, MHC-II, B220, and NK cells. Cells were then stained for CD8, CD44, CD62L, and CD127 and sorted (using a iCyt Reflection parallel cell sorter). Cells were collected and cultured (0.5 x106 cells/well) in 10% complete RPMI media supplemented with 0.005 ugr Con A and RNA prepared using TRIZOL and the 'RNeasy clean-up kit' (Invitrogen) after activation for different times. We established single transcriptional profiles for 6 time points after T cell activation (4, 6, 8, 16, 20, 24 h) including a control zero h time point (prior to activation). RNA was isolated by standard procedures and its quality was assessed by the NYU Center for Health Informatics and Bioinformatics. cDNAs were hybridized to GeneSpring arrays using the mouse genome MOE430 2.0 array (Affymetrix) which interrogates ~45,000 transcripts.

Background corr dist: KL-Divergence = 0.0627, L1-Distance = 0.0842, L2-Distance = 0.0115, Normal std = 0.6392

0.693 Kernel fit Pairwise Correlations Normal fit

Density 0.346

0.000 CEM 1

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

Pre-normalization Quantiles

CD8+ CentralConA-activated memoryConA-activated ConA-activatedT CD8+ cells CentralConA-activatedbefore CD8+ treatmentCentralConA-activatedmemory CD8+ CentralConA-activatedmemory CD8+T with cells ConCentralmemory CD8+atT cellsT4, A, biologicalCentralmemory CD8+atT cellsT6, Centralbiologicalmemory atT rep1 cellsT8, biologicalmemory(0.088599)[(0.126863) atT rep1mincellsT16, (0.079493) biologicalatT rep1cells T20,] (0.341223) biologicalat T24,rep1 biological(0.0805365)[ rep1 medium (0.167364) rep1 (0.115921) ] [ max ] CEM 1 Col6a2 3.3 3.3 63.6 P ( S | Z, I ) = 1.00 Col6a1 3.7 10.7 214.4 Mean Corr = 0.91388 Col6a3 4.7 11.0 59.0 Bgn 3.3 16.7 759.0 Sspn 3.3 11.7 106.9 Crispld2 3.3 15.7 337.0 Col1a2 19.1 23.4 1550.2 Col5a2 3.3 3.3 82.4 Col1a1 7.7 19.7 1693.9 Col5a1 3.3 30.8 212.7 Col3a1 6.4 24.1 154.9 CEM 1 + Sparc 3.3 15.1 1719.3 Top 10 Genes Pcolce 14.1 40.2 151.4 Mmp2 3.4 13.4 37.8 Fstl1 16.7 74.6 273.3 Ccdc80 3.3 22.8 91.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE11898" 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=GSE11898 Status: Public on Jun 27 2008 Title: Expression data from primary mesangial cells stimulated with DNA and RNA ligands Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21949095 Summary & Design: Summary: Extrarenal viral infections commonly trigger glomerulonephritis mostly in association with immune complex disease. The immunoglobulin component of immune complexes can activate glomerular cell Fc receptors but whether complexed viral nucleic acids contribute to glomerular inflammation remains unknown. Glomerular mesangial cells express TLR3 but lack TLR7-9, hence, it is unclear whether mesangial cells can recognize and respond to viral ssRNA or DNA. Here we studied the immune responses activated by 3P-RNA (5'Triphosphate RNA) and Non-CpG DNA (Double stranded DNA) in primary mesangial cells (PMC).

We used microarrays to detail the global programme of gene expression that induced by 3P-RNA and Non-CpG DNA.

Keywords: diffrent ligands

Overall design: PMC were stimulated with 3P-RNA and Non-CpG DNA for 6 hours and then total RNA was isolated for hybridization to MOE430_2 arrays.

Background corr dist: KL-Divergence = 0.0613, L1-Distance = 0.0257, L2-Distance = 0.0008, Normal std = 0.5353

0.763 Kernel fit Pairwise Correlations Normal fit

Density 0.382

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

lipofectaminelipofectamine atlipofectamine 6h-1 (0.150586)atNon-CpG 6h-2 (0.121594)atNon-CpG 6h-3 DNA (0.0853933) Non-CpGat DNA6h-1 3P-RNA(0.155648)at DNA6h-2 3P-RNA(0.133309)at at 6h-3 6h-1 3P-RNA(0.128281) (0.051133)at 6h-2 (0.0836784)at 6h-3 (0.0903768) [ min ] [ medium ] [ max ] CEM 1 Col6a2 13025.6 17521.1 19094.9 P ( S | Z, I ) = 1.00 Col6a1 13698.3 16961.0 20312.1 Mean Corr = 0.91328 Col6a3 11535.2 14459.4 15533.5 Bgn 18569.8 21032.0 25643.6 Sspn 975.5 1565.2 2825.2 Crispld2 38.3 68.0 127.4 Col1a2 14064.7 17056.1 20666.3 Col5a2 24516.0 26626.9 29471.9 Col1a1 18055.8 28483.1 35187.7 Col5a1 11804.1 12794.6 16673.0 Col3a1 5777.5 9345.8 11163.1 CEM 1 + Sparc 32671.9 34441.6 35656.2 Top 10 Genes Pcolce 24730.9 26295.8 27132.2 Mmp2 8978.0 11009.9 14363.1 Fstl1 20224.8 21369.1 23060.9 Ccdc80 9544.1 10364.2 11621.7

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE18281" 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=GSE18281 Status: Public on Nov 24 2009 Title: Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20064453 Summary & Design: Summary: Interaction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.

Overall design: 4 to 6 weeks old male C57bl6/J were used for microdissection of 3 thymic cortical subregions and thymic medulla or for sorting cortical and medullary thymocytes. These samples were used for subsequent RNA purification, labeling and hybridization to Affymetrix arrays

Background corr dist: KL-Divergence = 0.1533, L1-Distance = 0.0296, L2-Distance = 0.0018, Normal std = 0.3795

1.051 Kernel fit Pairwise Correlations Normal fit

Density 0.526

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

Sorted corticalSorted cortical Sortedthymocyte, cortical Sortedthymocyte, biological cortical Sortedthymocyte, biological corticalSortedrep1thymocyte, biological(0.0169385) medullarySortedrep2thymocyte, biological(0.0163582) medullarySortedrep3 thymocyte, biological(0.021826) medullarySortedrep4 thymocyte, (0.0238277) biologicalmedullarySortedrep5 thymocyte, (0.0174683) biologicalmedullaryMicrodissected rep1thymocyte, biologicalMicrodissected(0.0238446) rep2thymocyte, biologicalMicrodissected(0.0236687) sub-capsular rep3 biologicalMicrodissected(0.0243759) sub-capsular rep4 corticalMicrodissected(0.0241379) sub-capsular rep5 corticalMicrodissected(0.0216721) region,central cortical Microdissected region,biologicalcentralcortical Microdissected region,biologicalcentralcortical region, rep1Microdissected biologicalperi-medullarycortical (0.0153113)region,biological rep2Microdissected peri-medullary (0.0185453)region,biological rep3 rep1Microdissected peri-medullary(0.0171593)cortical biological(0.0166735) rep2Microdissected wholecortical region,(0.0219567) rep3 Microdissectedcortex, wholecortical region,biological(0.0212973) Microdissectedcortex,biological whole region,biological rep1 Microdissectedcortex,biological whole biological (0.0213589)rep1 rep2 Microdissectedcortex, biological(0.0426195)whole (0.0253965)rep2 rep3 Microdissectedcortex, biological(0.0340654)whole (0.0186424)rep3 Microdissectedcortex, biological(0.0258834)whole rep4 Microdissectedcortex, biological(0.0325094)whole rep5 Microdissectedmedulla, biological(0.0381026)whole rep6 Microdissectedmedulla, (0.0168288)whole biological rep7 Microdissectedmedulla, (0.0269017)whole biological rep1 Microdissectedmedulla, whole biological(0.0752008) rep2 medulla, whole biological(0.0564098) rep3 medulla, whole biological(0.0379852) rep4 medulla, biological(0.053768) rep5[ biological(0.0495943)min rep6 (0.049138) ]rep7 (0.0705337)[ medium ] [ max ] CEM 1 Col6a2 11.9 345.1 3109.3 P ( S | Z, I ) = 1.00 Col6a1 5.1 290.1 2827.6 Mean Corr = 0.91086 Col6a3 47.8 192.6 977.7 Bgn 3.4 310.6 2279.4 Sspn 1.7 81.5 325.7 Crispld2 41.6 187.2 487.3 Col1a2 2.6 131.4 395.8 Col5a2 3.5 219.3 1584.3 Col1a1 1.7 14.2 431.3 Col5a1 8.8 105.6 712.7 Col3a1 2.3 75.6 265.8 CEM 1 + Sparc 3.3 431.2 2058.3 Top 10 Genes Pcolce 2.3 207.5 966.2 Mmp2 7.6 602.0 1603.2 Fstl1 1.8 211.3 1720.8 Ccdc80 4.1 132.0 894.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE11759" 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=GSE11759 Status: Public on Dec 01 2008 Title: Role of HNF4alpha in the adult colon Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19898610 Summary & Design: Summary: Background & Aims: HNF4α is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4α deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4α. Methods: A conditional intestinal epithelial Hnf4α knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4α intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4α null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4α colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4α mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4α in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.

Overall design: HNF4alpha was conditionally knockout in the mouse epithelial colon with the villin CRE. A total of 3 control and 3 mutant littermates individuals were sacrificed at 1 year of age. The colon was harvested and Total RNA was isolated from each individuals. Each RNA sample was independently used to generate probes to screen affymetrix chips.

Background corr dist: KL-Divergence = 0.0312, L1-Distance = 0.0121, L2-Distance = 0.0001, Normal std = 0.6535

0.610 Kernel fit Pairwise Correlations Normal fit

Density 0.305

0.000 CEM 1

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

Pre-normalization Quantiles

mouse colon_hnf4mutant_rep1mouse colon_hnf4control_rep1mouse colon_hnf4control_rep2mouse colon_hnf4control_rep3mouse (0.116229) colon_hnf4mutant_rep2mouse (0.158407) colon_hnf4mutant_rep3 (0.157802) (0.183084) (0.29958)[ (0.0848977)min ] [ medium ] [ max ] CEM 1 Col6a2 677.3 3746.6 5777.9 P ( S | Z, I ) = 1.00 Col6a1 276.8 2556.9 4484.9 Mean Corr = 0.90770 Col6a3 159.8 1523.9 2067.2 Bgn 121.1 2413.4 2741.4 Sspn 49.8 524.0 624.8 Crispld2 132.1 560.4 679.3 Col1a2 86.2 689.4 1045.5 Col5a2 148.5 739.5 870.6 Col1a1 161.5 1442.1 2139.7 Col5a1 112.6 522.4 675.6 Col3a1 34.2 264.1 422.3 CEM 1 + Sparc 411.1 2589.2 3479.8 Top 10 Genes Pcolce 232.2 879.4 938.4 Mmp2 85.8 1102.2 1389.3 Fstl1 105.8 747.1 781.2 Ccdc80 287.9 857.2 1047.5

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE37191" 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=GSE37191 Status: Public on Jan 01 2013 Title: Gene expression profiling reveals mast cell-dependent inflammation in the meninges in early EAE. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23267561 Summary & Design: Summary: The meninges are generally considered relatively inert tissues that house the CSF and provide protection for the brain and spinal cord. However, our previous studies using Kit mutant (Kit W/Wv) mast cell-deficient mice demonstrated that mast cells residing in the dura mater and pia mater exacerbate the severity of experimental autoimmune encephalomyelitis (EAE), the rodent model of the CNS demyelinating disease, multiple sclerosis. These data suggest that the meninges are sites of active immune responses in disease. Gene expression profiles of meningeal tissue from wild type and mast cell deficient mice prior to and at day 6 post-EAE induction were found highly distinct. Increases in both mast cell- and neutrophil-associated transcripts were among the notable disease-related changes observed in wild type mice. Kinetic analyses show that meningeal mast cells are activated within 24 hours of disease induction to express multiple mediators including IL-1b and TNF as well as the neutrophil chemoattractant, CXCL2, an observation corresponding with an influx of neutrophils to the meninges. Neutrophil recruitment as well as the disease-related loss of BBB integrity is dependent on mast cell-derived TNF. These data provide unequivocal evidence that the meninges are sites of early inflammatory events in EAE. Mast cells residing within these tissues promote disease by orchestrating an early and efficient immune cell co-localization resulting in a robust local inflammatory response and a breach of the proximal BBB. We hypothesize that these events reflect an aberrant manifestation of the normal immune surveillance role of the meninges in infection settings.

Overall design: Immunized WT and Kit W/Wv mice were sacrificed on Day 6 post-immunization and perfused with PBS as were naïve littermate control mice. The dura mater was immediately removed from the calvarium of the skull and pooled (10 mice/group, 4 groups). RNA was isolated using SV Total RNA Isolation System (Promega). Each pool was analyzed in technical triplicates. Briefly, cRNA was synthesized and amplified/labeled using the Affymetrix Express Kit, then fragmented and hybridized to the The GeneChip® Mouse Genome 430 2.0 Array in accordance to the Affymetrix GeneChip expression analysis technical manual (Affymetrix, Santa Clara, CA). After hybridization, arrays were washed and stained with Affymetrix fluidics protocol FS450_0001 and scanned with a 7G Affymetrix GeneChip Scanner. Image data were analyzed with Affymetrix Expression Console¢ software and normalized with Robust Multichip Analysis (RMA; www.bioconductor.org/) to determine signal log ratios (CITE: Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5, R80.). The mean fold change was calculated from 3 independent technical replicates for each of the four experimental conditions and assessed by a non-parametric rank product test (CITE: Hong, F., Breitling, R., McEntee, C.W., Wittner, B.S., Nemhauser, J.L., and Chory, J. (2006). RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 22, 2825-2827). Heat maps were generated with Genesis (Cite: Sturn, A., Quackenbush, J. and Trajanoski, Z. (2002) Genesis: cluster analysis of microarray data. Bioinformatics, 18, 207-208).

Background corr dist: KL-Divergence = 0.1081, L1-Distance = 0.0249, L2-Distance = 0.0009, Normal std = 0.4256

0.937 Kernel fit Pairwise Correlations Normal fit

Density 0.469

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 mouseWT duramouseWT mater, duramouseWT EAE,mater, duramouse technicalWT EAE,mater, duramouse technicalWT EAE,replicatemater, duramouse technicalKit naïvereplicatemater, 1 W/Wvdura (0.0926205)Kit control,naïvereplicatemater, mouse 2W/Wv (0.0642655)Kit control,naïve technicalduramouse 3W/Wv (0.0824193) mater,Kit control, technicalduramouse W/Wv replicate EAE,mater,Kit technicalduramouse W/Wv replicate technical 1 EAE,mater,Kit(0.0843328) duramouse W/Wv replicate technical 2 EAE, replicatemater,(0.0712948) duramouse technical 3 naïve replicatemater,(0.0864744) 1 dura (0.0946064) control,naïvereplicatemater, 2 (0.0831578) control,naïve technical[ 3 min(0.0803648) control, technical replicate ] technical replicate 1 (0.12241) replicate[ 2 medium(0.0631177) 3 (0.0749358) ] [ max ] CEM 1 Col6a2 13531.2 15249.3 19028.0 P ( S | Z, I ) = 1.00 Col6a1 9577.7 12211.3 13854.3 Mean Corr = 0.90643 Col6a3 9375.9 11918.9 12922.9 Bgn 22387.6 27559.8 29598.6 Sspn 1484.4 1810.3 2122.4 Crispld2 3805.1 5234.3 5488.5 Col1a2 30470.9 35409.6 37996.7 Col5a2 15143.8 18448.8 20098.3 Col1a1 8595.8 10089.0 11593.9 Col5a1 4137.6 5126.4 5505.2 Col3a1 4192.0 5165.3 5646.6 CEM 1 + Sparc 33098.9 37195.9 39869.7 Top 10 Genes Pcolce 13621.1 16393.4 18561.8 Mmp2 5318.0 6863.0 7384.2 Fstl1 7058.3 8020.9 9512.1 Ccdc80 6579.9 9651.3 10540.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE48790" 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=GSE48790 Status: Public on Jul 12 2013 Title: Expression data from GTF2i mutated ES cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23831514 Summary & Design: Summary: Data present the expression analysis of different mouse ES cell line with altered expression of GTF2I.

Overall design: We used microarrays to detail the global programme of gene expression underlying altered expression of GTF2I and identified distinct classes of deregulated genes

Background corr dist: KL-Divergence = 0.0303, L1-Distance = 0.0391, L2-Distance = 0.0018, Normal std = 0.6989

0.613 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

HPRTKO,HPRTKO, biologicalGTF2iTrap biological rep1GTF2iTrap (0.152175)line, rep2Wild-type, biological (0.184734)line,Wild-type, biological biological rep Gtf2i1 (0.116372) biological rep Mutant rep1 Gtf2i2 (0.0889438) (0.131989) Mutantline, rep2 biological (0.147341) line, biological rep 1 (0.0915457) rep[ 2min (0.0868998) ] [ medium ] [ max ] CEM 1 Col6a2 163.8 3497.8 4448.6 P ( S | Z, I ) = 1.00 Col6a1 68.3 3605.6 4651.4 Mean Corr = 0.90474 Col6a3 122.6 4966.7 5412.9 Bgn 740.8 18964.4 21544.2 Sspn 36.6 410.3 463.6 Crispld2 51.9 292.7 426.7 Col1a2 617.4 18160.7 23994.1 Col5a2 996.3 18456.4 27564.8 Col1a1 132.9 5552.2 7522.3 Col5a1 306.3 6285.9 8373.3 Col3a1 56.6 6776.9 9944.5 CEM 1 + Sparc 5465.7 21496.7 26272.4 Top 10 Genes Pcolce 2550.3 11080.2 12119.5 Mmp2 404.4 5066.4 6066.0 Fstl1 1992.8 13376.7 20660.7 Ccdc80 220.2 2378.8 5069.4

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE54207" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.781 Kernel fit Pairwise Correlations Normal fit

Density 0.391

0.000 CEM 1

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

Pre-normalization Quantiles

E11.5 AE12.5 (0.0968301) AE14.5 (0.0563284) AE11.5 (0.208625) BE12.5 (0.114429) BE14.5 (0.0527522) BE11.5 (0.134104) CE12.5 (0.0788567) CE14.5 (0.115389) C (0.142687) [ min ] [ medium ] [ max ] CEM 1 Col6a2 952.4 2664.2 13770.2 P ( S | Z, I ) = 1.00 Col6a1 343.0 1233.0 9410.1 Mean Corr = 0.90420 Col6a3 788.8 3101.3 17028.9 Bgn 456.5 1022.5 12732.5 Sspn 105.8 450.0 1291.5 Crispld2 179.4 271.6 421.8 Col1a2 7042.4 10434.6 27059.8 Col5a2 4096.7 6503.5 20663.4 Col1a1 327.3 759.4 9075.3 Col5a1 1910.2 3925.6 16773.5 Col3a1 3752.1 6698.4 18332.1 CEM 1 + Sparc 1330.1 5295.0 23393.2 Top 10 Genes Pcolce 4305.6 4684.0 10918.9 Mmp2 3594.7 4304.9 8632.6 Fstl1 6826.5 12752.5 23609.5 Ccdc80 847.8 1952.1 3455.8

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE25029" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 56 -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=GSE25029 Status: Public on Jul 01 2011 Title: Ionizing radiation in GI tract of Tweak KO mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21893119 Summary & Design: Summary: TWEAK/Fn14 signaling may regulate the expression of genes involved in epithelial repair and mucosal inflammation. Comparing the gene signatures in WT and TWEAK KO mice will inform the biology of TWEAK/Fn14 pathway in the GI tract.

Overall design: Mice were treated with 3 Gy of ionizing radiation. After 6h and 24h mice were sacrificed, and whole colon and jejunum were harvested, and RNA was isolated from these tissues. Each CEL file represents a different mouse.

Background corr dist: KL-Divergence = 0.0433, L1-Distance = 0.0713, L2-Distance = 0.0046, Normal std = 0.9679

0.480 Kernel fit Pairwise Correlations Normal fit

Density 0.240

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_Col_0h_1WT_Col_6h_1 (0.0154088)WT_Col_24h_1 (0.0140016)WT_Col_0h_2WT_Col_6h_2 (0.0176596) (0.0104114)WT_Col_24h_2 (0.0145786)WT_Col_0h_3WT_Col_24h_3 (0.0160474) (0.015847)WT_Col_0h_4WT_Col_6h_4 (0.0167894) (0.0137869)WT_Col_0h_5 (0.0140207)WT_Col_6h_5 (0.012823)WT_Col_24h_5 (0.0124254)KO_Col_0h_1KO_Col_6h_1 (0.0124921) (0.0152639)KO_Col_24h_1 (0.0200827)KO_Col_0h_2 KO_Col_6h_2(0.0159739) (0.0152606)KO_Col_24h_2 (0.0141169)KO_Col_0h_3 KO_Col_6h_3(0.0240036) (0.0154498)KO_Col_24h_3 (0.0114421)KO_Col_0h_4 KO_Col_6h_4(0.0175176) (0.0190076)KO_Col_24h_4 (0.0292844)KO_Col_0h_5 KO_Col_6h_5(0.024034) (0.0146613)KO_Col_24h_5 (0.0145792)WT_Jej_0h_1 WT_Jej_6h_1(0.0229694) (0.0175333)WT_Jej_24h_1 (0.0308141)WT_Jej_0h_2 WT_Jej_6h_2(0.0185586) (0.01909)WT_Jej_24h_2 (0.0466382)WT_Jej_0h_3 WT_Jej_6h_3(0.0196371) (0.0167107)WT_Jej_24h_3 (0.012267)WT_Jej_0h_4 WT_Jej_6h_4(0.0160803) (0.0153278)WT_Jej_24h_4 (0.017905)WT_Jej_0h_5 WT_Jej_6h_5(0.0170369) (0.0193559)KO_Jej_0h_1 (0.0527844)KO_Jej_6h_1 (0.0148759)KO_Jej_24h_1 (0.0112114)KO_Jej_0h_2 KO_Jej_24h_2(0.0108801) (0.0186004)KO_Jej_0h_3 KO_Jej_6h_3(0.0146921) (0.0216076)KO_Jej_24h_3 (0.0117914)KO_Jej_0h_4 KO_Jej_6h_4(0.010433) (0.0134699)KO_Jej_24h_4 (0.032094)KO_Jej_0h_5 KO_Jej_6h_5(0.0136751) (0.0168993)KO_Jej_24h_5 (0.0152474) (0.014844) [ min ] [ medium ] [ max ] CEM 1 Col6a2 189.9 1371.5 2809.1 P ( S | Z, I ) = 1.00 Col6a1 320.9 2411.4 5845.1 Mean Corr = 0.89734 Col6a3 318.4 1810.1 4240.4 Bgn 401.1 1447.1 3566.5 Sspn 41.5 535.2 1073.5 Crispld2 94.2 382.6 1226.2 Col1a2 246.1 1598.6 5002.3 Col5a2 210.6 2141.4 5445.1 Col1a1 283.6 1862.1 7174.8 Col5a1 172.6 844.9 2210.6 Col3a1 122.9 1245.7 5698.9 CEM 1 + Sparc 1538.5 4818.0 15259.7 Top 10 Genes Pcolce 200.2 912.7 2541.9 Mmp2 84.4 524.6 2566.9 Fstl1 331.4 1819.7 4553.1 Ccdc80 71.0 439.1 1601.0

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE28277" 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=GSE28277 Status: Public on Jun 01 2011 Title: Altered Gene Expression in Placentae from a Mouse Model of Diabetic Pregnancy Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21491160 Summary & Design: Summary: AIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, such as metabolic syndrome and hypertension. We hypothesized that adverse outcomes from diabetic pregnancies may be linked to compromised placental function. Our goal in this study was to identify cellular and molecular abnormalities in diabetic placenta.

METHODS: Using a mouse model of diabetic pregnancy, placental gene expression was assayed at midgestation and cellular composition was analyzed at various stages. Genome-wide expression profiling was validated by quantitative PCR, and tissue localization studies were performed to identify cellular correlates of altered gene expression in diabetic placenta.

RESULTS: We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal as well as those in the embryonic compartments. We also found altered cellular composition of the decidual compartment. Furthermore, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells.

CONCLUSIONS/INTERPRETATION: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of both embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and placenta overall. Whether these changes represent direct responses to hyperglycaemia or physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and have implications for developmental origins of adult disease.

Overall design: The STZ diabetic mouse model was used to investigate gene expression changes in diabetic placentae at E10.5. Placentae were dissected from 5 different FVB dams at embryonic day 10.5 under diabetic conditions and from 5 control dams. Gene expression profiles from five individual placentae from independent pregnancies per group were compared.

Background corr dist: KL-Divergence = 0.0896, L1-Distance = 0.0222, L2-Distance = 0.0008, Normal std = 0.4569

0.873 Kernel fit Pairwise Correlations Normal fit

Density 0.437

0.000 CEM 1

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

Pre-normalization Quantiles

ControlControl 1 (0.0593952)Control 2 (0.0521207)Control 3 (0.247725)Control 4 (0.111034)Experimental 5 (0.0509233)Experimental 1Experimental (0.122288) 2Experimental (0.120607) 3Experimental (0.0950922) 4 (0.0733854) 5 (0.0674287) [ min ] [ medium ] [ max ] CEM 1 Col6a2 206.9 366.7 7540.7 P ( S | Z, I ) = 1.00 Col6a1 245.2 414.1 5813.1 Mean Corr = 0.89720 Col6a3 716.4 1427.0 9331.1 Bgn 1045.7 2083.0 9133.2 Sspn 5.0 19.5 122.7 Crispld2 622.3 827.7 1671.3 Col1a2 862.1 1574.1 11592.2 Col5a2 11266.3 14037.7 20236.8 Col1a1 525.0 1076.9 12519.0 Col5a1 388.8 777.7 3481.3 Col3a1 342.1 861.4 3011.2 CEM 1 + Sparc 22101.4 28684.6 35880.4 Top 10 Genes Pcolce 376.2 891.7 6883.9 Mmp2 626.9 1117.8 2876.4 Fstl1 21384.7 26809.3 30322.3 Ccdc80 127.2 184.4 3018.4

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE18534" 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=GSE18534 Status: Public on Jun 01 2010 Title: Mouse small cell lung cancer model Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20406986 Summary & Design: Summary: A mouse model for human small cell lung carcinoma (SCLC) has been developed based on evidence in human tumors that the tumor suppressor functions of RB and p53 are defective in more than 90% of SCLC cases. We also developed another mouse model also combines loss of p130 (Rbl2), an RB-related gene, with deletion of RB and p53. These two mouse tumors were shown to closely resemble human SCLC.

Overall design: The goal of this array experiment is to assess genome-wide gene expression of those mouse tumors and determine the similarity of the mouse models to human SCLC. Gene expression from Mouse Rb/p53 ( n=10 ) and Rb/p53/p130 primary tumors ( n=3 ) as well as tumor-free adult mouse lungs ( n=2 ) was measured using the Affymetrix GeneChip Mouse Genome 430-2.0 arrays.

Background corr dist: KL-Divergence = 0.0991, L1-Distance = 0.0337, L2-Distance = 0.0022, Normal std = 0.4651

0.881 Kernel fit Pairwise Correlations Normal fit

Density 0.440

0.000 CEM 1

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

Pre-normalization Quantiles

double doubleknockout doubleknockout lung doubleknockoutcancer lung doubleknockout-cancer 1 lung(0.0748788) doubleknockout-cancer 2 lung(0.05666) doubleknockout-cancer 3 lung(0.0472245) doubleknockout-cancer 4 lung(0.026446) doubleknockout-cancer 5 lung(0.0604177) doubleknockout-cancer 6 lung(0.0285949) normalknockout-cancer 7 lung(0.0582678) normal-cancerlung 8 lung(0.0986139) - 1 triple-cancerlung (0.148672)9 (0.0520427) -knockout 2 triple- (0.207621)10 (0.0422889) knockouttriple lung knockoutcancer lung -cancer 11 lung (0.0293119) -cancer 12 (0.0305702) - 13[ (0.0383902)min ] [ medium ] [ max ] CEM 1 Col6a2 348.8 508.7 3064.0 P ( S | Z, I ) = 1.00 Col6a1 268.5 577.3 2486.5 Mean Corr = 0.89491 Col6a3 388.4 713.1 2524.9 Bgn 1746.4 3671.1 11383.0 Sspn 160.6 437.4 1552.8 Crispld2 55.1 120.0 1655.1 Col1a2 674.9 970.3 2452.3 Col5a2 1086.3 1606.5 3229.6 Col1a1 146.9 239.5 881.6 Col5a1 103.0 187.5 745.7 Col3a1 248.4 449.3 804.9 CEM 1 + Sparc 3454.0 5067.9 13763.8 Top 10 Genes Pcolce 483.0 833.2 4941.7 Mmp2 115.8 238.8 665.0 Fstl1 969.1 1342.1 2317.4 Ccdc80 310.4 569.0 1191.1

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE27987" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 31 -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=GSE27987 Status: Public on Aug 25 2011 Title: Differential pre-mRNA processing in Crebbp+/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21901164 Summary & Design: Summary: The presence of unspliced transcripts in hematopoietic stem cells (HSCs) and the proposed association of CREBBP with the constitutive production of unspliced RNA and with pre-mRNA processing prompted us to examine more closely an anomaly we had noted in microarray-based gene expression studies but had previously attributed to experimental noise. We noticed that more than half of the probe sets down-regulated in Crebbp+/- fetal liver HSCs (FLHSCs) relative to wild-type (WT) mapped entirely within introns, rather than detecting exonic or spliced sequences. We therefore set out to test whether this might be evidence that reduced CREBBP levels selectively alter the generation of full-length, unspliced pre-mRNA. We also asked whether this process might be associated with differentiation since self-renewal and lineage commitment are the both responses for which HSCs are primed.

Overall design: cell type comparison

Background corr dist: KL-Divergence = 0.0422, L1-Distance = 0.0924, L2-Distance = 0.0091, Normal std = 0.9341

0.496 Kernel fit Pairwise Correlations Normal fit

Density 0.248

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

Crebbp CrebbpwtHSC CrebbpsamplewtHSC Crebbp samplewtHSC1 replicate Crebbp samplewtHSC1 replicate 1 (0.0297531) Crebbp samplehetHSC2 replicate 2 (0.0182109) Crebbp hetHSC 2sample replicate 1 (0.0258065) CrebbphetHSC sample1 replicate 2 (0.0277878) Ep300hetHSC sample1 replicate 1 wtHSC(0.0272306)Ep300 sample2 replicate 2 samplewtHSC(0.0149957)Ep300 2 replicate 1 samplewtHSC(0.0197387)1Ep300 replicate 2 samplewtHSC(0.0197936)1Ep300 replicate 1 (0.0201775) samplehetHSC2Ep300 replicate 2 (0.0162463) hetHSC 2Ep300sample replicate 1 (0.0111579) hetHSC Ep300sample1 replicate 2 (0.0162016) hetHSC Cdkn1asample1 replicate 1 (0.0133511) Cdkn1asample2wtHSC replicate 2 (0.0125776) Cdkn1a21wtHSC replicate(0.0397592) 1 (0.0140639)Cdkn1a 2wtHSC (0.0388015) 2 (0.0147401)Cdkn1a 3nullHSC (0.107862)Cdkn1a nullHSC 1 (0.0409494)Cdkn1a nullHSC 2 (0.0424193)Crebbp nullHSC 3 (0.0456696) CrebbpwtMEF 4 (0.0444545) Crebbp1wtMEF (0.0606214) Crebbp2wtMEF (0.036955) Crebbp3wtMEF (0.0489333) Crebbp4hetMEF (0.0391962) CrebbphetMEF 1 (0.033182) CrebbphetMEF 2 (0.0405623) hetMEF 3 (0.0422345) 4 (0.0365666) [ min ] [ medium ] [ max ] CEM 1 Col6a2 1.9 13.0 19954.0 P ( S | Z, I ) = 1.00 Col6a1 2.0 13.2 21980.5 Mean Corr = 0.89298 Col6a3 1.8 13.0 19768.8 Bgn 1.8 13.1 38855.1 Sspn 2.0 13.3 1930.7 Crispld2 57.9 84.6 693.6 Col1a2 2.2 13.8 38747.5 Col5a2 2.0 13.5 45077.2 Col1a1 2.2 14.7 106081.8 Col5a1 2.1 14.2 28199.6 Col3a1 2.0 13.9 13911.0 CEM 1 + Sparc 2.4 13.2 50990.3 Top 10 Genes Pcolce 2.2 14.6 40705.5 Mmp2 2.4 15.4 7706.9 Fstl1 221.4 732.3 47954.8 Ccdc80 2.1 13.8 17388.2

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip GEO Series "GSE34552" 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=GSE34552 Status: Public on Nov 05 2012 Title: Expression data from mouse kidney tissue Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22791343 Summary & Design: Summary: The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage.

This is a comparison between the renin inhibitor aliskiren with the At1 antagonist losartan in mice with chronic kidney disease due to renal ablation.

Overall design: Renal tissue from ablated mice was used after 6-week treatment with either 500 mg/l losartan or 50 mg/kg aliskiren per day (n = 5)

Background corr dist: KL-Divergence = 0.0759, L1-Distance = 0.0208, L2-Distance = 0.0006, Normal std = 0.4855

0.822 Kernel fit Pairwise Correlations Normal fit

Density 0.411

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

Kidney Kidneytissue after Kidneytissue losartan after Kidneytissue losartan treatment after Kidneytissue losartan treatment after Kidneytissue mouse losartan treatment after Kidneytissue 1mouse (0.0592359) losartan treatment after Kidneytissue 2mouse (0.0752839) aliskiren treatment after Kidneytissue 3mouse (0.31885) aliskiren treatment after Kidneytissue 4mouse (0.10835) aliskiren treatment after tissue 5mouse (0.103686) aliskiren treatment after 1mouse (0.0913257) aliskiren treatment 2mouse (0.0641191) treatment[ 3mouse min(0.04574) 4mouse (0.0560079) ] 5 (0.0774009)[ medium ] [ max ] CEM 1 Col6a2 303.0 451.9 864.5 P ( S | Z, I ) = 1.00 Col6a1 137.4 208.0 445.3 Mean Corr = 0.89281 Col6a3 371.3 668.4 1431.0 Bgn 1023.2 1455.6 3962.2 Sspn 33.6 44.9 161.1 Crispld2 145.8 229.7 394.8 Col1a2 108.3 302.1 1750.9 Col5a2 125.9 229.7 1396.3 Col1a1 70.1 87.6 177.3 Col5a1 58.1 117.7 333.2 Col3a1 23.9 101.0 527.6 CEM 1 + Sparc 690.3 1271.1 4426.9 Top 10 Genes Pcolce 1552.9 1871.9 3005.6 Mmp2 108.7 149.2 555.1 Fstl1 317.8 493.4 1703.7 Ccdc80 139.8 207.2 1375.6

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip 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 (0.0883531) Control 2 Liver(0.0682501) Experiment 3 Liver(0.0765577) ExperimentLiver 1 (0.0830733) ControlMuscle 2 (0.0735256) 1 MuscleControl(0.0987677) MuscleControl 1 (0.0762835) MuscleControl 2 (0.059911) MuscleExperiment 3 (0.0842071) MuscleExperiment 1 (0.0636638) Experiment 2 (0.111338) 3 (0.116069)[ min ] [ medium ] [ max ] CEM 1 Col6a2 29.4 5688.9 13742.2 P ( S | Z, I ) = 1.00 Col6a1 151.0 4899.1 10123.8 Mean Corr = 0.89005 Col6a3 307.6 3455.6 7402.5 Bgn 2142.7 3561.3 9365.6 Sspn 126.7 5895.0 6800.7 Crispld2 46.8 946.6 1567.4 Col1a2 34.1 5860.5 37601.8 Col5a2 19.0 1813.1 5069.9 Col1a1 19.0 7733.4 47939.6 Col5a1 218.8 1749.1 3192.8 Col3a1 49.0 969.9 2869.1 CEM 1 + Sparc 1403.6 19410.8 49763.8 Top 10 Genes Pcolce 175.5 1944.6 8011.6 Mmp2 233.8 2669.6 5039.3 Fstl1 79.0 2585.4 5612.7 Ccdc80 337.5 1470.6 2644.2

Null module Aimp1 Cav2 Bloc1s6 Stx2 Nrsn1 Ap1g2 Yipf2 Pcsk1 Gnas Nptx1 Ap3s1 Nts Prg2 1500015O10Rik Tmem168 Plekhf2 Yipf1 Ovgp1 Bloc1s3 Shh Pcsk2 Galnt15 Syt13 Rab11a Nrsn2 Aph1b Vgf Exoc3l Cnst Astl Cdk16 B230216G23Rik Yipf3 Ap1ar Cpa3 Bloc1s5 Rab3d Hck Pigr 0610007P14Rik Myrip