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

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

Dataset: Num of genes in input gene set: 9 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. Bbip1 Num ofGenesinQueryGeneset:9.CEMs:1. Overview ofCo-ExpressionModules(CEMs) with DatasetWeighting Bbs7 Bbs4 Bbs9 Bbs5 Bbs2 Bbs1 Ttc8 Arl6

Arl6 Ttc8 Bbs1 Bbs2 Bbs5 Bbs9 Bbs4 Bbs7 Bbip1 Singletons CEM 1(94datasets) 0.0 Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 D430042O09Rik 1110051M20Rik 2610301B20Rik 1700029J07Rik Symbol Num ofCEMGenes:7.Predicted98.SelectedDatasets:94.Strength:1.2 CEM 1,Geneset"[G]BBSome",Page1 Tmem107 Tmem231 Tmem218 Tmem237 Fam229b Fam216a Dync2h1 Ccdc181 Ccdc173 Ccdc104 Dync2li1 Cep290 Dyx1c1 Cluap1 Spata7 Pcnxl4 Ttc30b Nphp1 Wdr60 Wdr78 Wdr34 Wdr19 Rab28 Pde6d Cep19 Crocc Pacrg Stk30 Tctn2 Ift122 Ttc26 Dpcd B9d1 Bbs4 Bbs9 Bbs5 Bbs2 Bbs1 Rpgr Lca5 Ift88 Ift80 Ift74 Ttc8 Arl3 Arl6 0.0 1.0

GSE23895 [18] GSE26299 [108]

GSE29318 [9] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE9441 [36] GSE13106 [10] GSE31972 [6] GSE48338 [8] GSE42601 [6] GSE22824 [24] GSE21900 [12] GSE6540 [12] GSE41759 [14] GSE24512 [29] GSE27605 [8] GSE36833 [49] GSE24813 [10] GSE21568 [12] GSE16675 [72] GSE47196 [6] GSE27630 [8] GSE40087 [15] GSE31561 [36] GSE19204 [6] GSE31797 [6] GSE39621 [51] GSE13526 [6] GSE23408 [39] GSE9954 [70] GSE19534 [26] GSE26745 [24] GSE39458 [6] GSE13302 [30] GSE14007 [8] GSE20696 [8] GSE40856 [8] GSE29685 [132] GSE26096 [10] GSE11201 [18] GSE17096 [20] GSE5671 [18] GSE51365 [28] GSE15610 [12] GSE16585 [31] GSE27546 [51] GSE37546 [20] GSE32095 [24] GSE34423 [40] GSE11870 [6] GSE4481 [18] GSE24207 [73] GSE28621 [21] GSE11291 [60] GSE39391 [21] GSE6675 [8] GSE46211 [18] GSE16496 [102] GSE54056 [12] GSE32529 [224] GSE1986 [17] GSE1871 [12] GSE7309 [12] GSE27675 [14] GSE40156 [42] GSE32986 [18] GSE10246 [182] GSE17097 [20] GSE37431 [6] GSE11898 [9] GSE27713 [7] GSE25778 [6] GSE44101 [6] GSE19073 [6] GSE8682 [8] GSE7863 [16] GSE33156 [18] GSE27261 [8] GSE28559 [30] GSE25088 [24] GSE56777 [8] GSE59437 [30] GSE13044 [59] GSE25257 [6] GSE13807 [10] GSE5127 [18] GSE14243 [6] GSE21247 [60] GSE8960 [18] GSE25423 [10] GSE6676 [8] GSE41342 [26] GSE15872 [18] GSE10528 [6] GSE43381 [26] GSE34091 [8] GSE10912 [6] GSE33770 [8] GSE23200 [6] GSE27717 [11] GSE9338 [42] GSE42061 [12] GSE21861 [8] GSE11862 [6] GSE17553 [16] GSE52474 [154] GSE5861 [6] GSE17797 [19] GSE27568 [16] GSE10965 [8] GSE7598 [8] GSE20335 [8] GSE27451 [6] GSE21193 [10] GSE19091 [6] GSE31849 [18] GSE34723 [101] GSE23081 [6] GSE27378 [8] GSE38672 [6] GSE42047 [24] GSE7596 [6] GSE5333 [16] GSE5313 [6] GSE6487 [30] GSE13490 [15] GSE25244 [9] GSE34206 [8] GSE12498 [12] GSE46443 [12] GSE8621 [12] GSE34279 [30] GSE43779 [6] GSE9061 [6] GSE34618 [7] GSE16751 [6] GSE10290 [24] GSE41907 [7] GSE47421 [24] GSE51804 [10] GSE9038 [24] GSE43059 [8] GSE24695 [9] GSE21842 [8] GSE40377 [42] GSE18907 [12] GSE7838 [9] GSE30488 [52] GSE7275 [8] GSE5582 [6] GSE14004 [9] GSE46094 [10] GSE40282 [6] GSE29081 [6] GSE13402 [7] GSE28731 [10] CEM+ CEM GSE39442 [11] GSE9725 [16] GSE5891 [6] GSE33308 [10] GSE31150 [6] GSE30852 [6] 0.0 GSE44175 [18] GSE28457 [24]

GSE50603 [12] Scale ofaveragePearsoncorrelations GSE30855 [6] GSE21393 [6] GSE56492 [12] GSE36229 [14] GSE3463 [12] GSE22371 [6] 0.2 GSE42548 [29] GSE27799 [6] GSE11990 [20] GSE2197 [6] GSE12769 [20] GSE6846 [6] GSE18326 [8] GSE4193 [8] GSE38831 [7] 0.4 GSE21299 [12] GSE1074 [12] GSE45820 [6] GSE13033 [6] GSE34002 [9] GSE29241 [6] GSE25029 [56] GSE27395 [12] GSE37316 [31] 0.6 GSE48790 [8] GSE28035 [9] GSE7685 [12] GSE12993 [6] GSE9247 [15] GSE17263 [6] GSE7424 [8] GSE15062 [21] GSE5309 [7] 0.8 GSE7707 [18] GSE43928 [12] GSE15318 [24] GSE4535 [6] Score 22.16 22.47 22.51 22.71 24.10 24.40 25.73 25.80 26.06 27.21 28.45 29.05 29.41 29.99 30.15 31.71 32.38 32.45 32.64 32.73 33.24 34.03 36.67 36.94 38.29 38.43 39.00 39.31 40.87 41.13 42.00 43.15 43.18 45.79 45.88 49.18 50.56 52.93 53.31 54.14 54.87 56.54 58.35 1.0 Notes Symbol Num ofCEMGenes:7.Predicted98.SelectedDatasets:94.Strength:1.2 CEM 1,Geneset"[G]BBSome",Page2 BC022687 AK129341 Fam179b Tctex1d2 Ankdd1b Ccpg1os Hist3h2a Ccdc157 Ccdc126 Tbc1d32 Tbc1d19 Traf3ip1 Ttc30a1 Pcmtd2 Cc2d2a Dzank1 Scaper Klhdc1 Efcab7 Pih1d2 Spice1 Tspyl4 Glt8d1 Map10 Wdr17 Wdr47 Wdr31 Pcbp3 Bbs12 Spa17 Snx14 Tusc3 Ndrg3 Cetn4 Trpc1 Nicn1 Dnal4 Rabl2 Nme5 Lekr1 Stk36 Tctn3 Mks1 Gas8 Triqk Ppil6 Nek4 Mlh3 Ift57 Kif9 0.0 1.0

GSE23895 [18] GSE26299 [108]

GSE50603 [12] Scale ofaveragePearsoncorrelations GSE30855 [6] GSE21393 [6] GSE56492 [12] GSE36229 [14] GSE3463 [12] GSE22371 [6] 0.2 GSE42548 [29] GSE27799 [6] GSE11990 [20] GSE2197 [6] GSE12769 [20] GSE6846 [6] GSE18326 [8] GSE4193 [8] GSE38831 [7] 0.4 GSE21299 [12] GSE1074 [12] GSE45820 [6] GSE13033 [6] GSE34002 [9] GSE29241 [6] GSE25029 [56] GSE27395 [12] GSE37316 [31] 0.6 GSE48790 [8] GSE28035 [9] GSE7685 [12] GSE12993 [6] GSE9247 [15] GSE17263 [6] GSE7424 [8] GSE15062 [21] GSE5309 [7] 0.8 GSE7707 [18] GSE43928 [12] GSE15318 [24] GSE4535 [6] Score 2.69 2.90 3.11 3.94 4.19 4.36 4.76 4.94 5.48 5.82 6.01 6.27 6.69 6.70 6.76 7.10 8.28 8.58 9.01 9.23 9.53 9.59 9.94 10.58 10.92 11.41 12.43 12.69 12.71 12.81 13.06 13.14 13.67 13.73 13.89 14.63 15.43 15.49 16.23 17.08 17.95 18.35 18.86 19.80 19.84 20.46 21.15 21.31 21.45 21.84 1.0 Notes Symbol Num ofCEMGenes:7.Predicted98. ofSelectedDatasets:94.CEMStrength:1.2 CEM 1,Geneset"[G]BBSome",Page3 AI429214 Ankrd42 Ccp110 Zc3h6 Nme7 0.0 1.0

GSE23895 [18] GSE26299 [108]

GSE29318 [9] Only showingfirst200datasets-Seetxtoutputforfulldetails . GSE9441 [36] GSE13106 [10] GSE31972 [6] GSE48338 [8] GSE42601 [6] GSE22824 [24] GSE21900 [12] GSE6540 [12] GSE41759 [14] GSE24512 [29] GSE27605 [8] GSE36833 [49] GSE24813 [10] GSE21568 [12] GSE16675 [72] GSE47196 [6] GSE27630 [8] GSE40087 [15] GSE31561 [36] GSE19204 [6] GSE31797 [6] GSE39621 [51] GSE13526 [6] GSE23408 [39] GSE9954 [70] GSE19534 [26] GSE26745 [24] GSE39458 [6] GSE13302 [30] GSE14007 [8] GSE20696 [8] GSE40856 [8] GSE29685 [132] GSE26096 [10] GSE11201 [18] GSE17096 [20] GSE5671 [18] GSE51365 [28] GSE15610 [12] GSE16585 [31] GSE27546 [51] GSE37546 [20] GSE32095 [24] GSE34423 [40] GSE11870 [6] GSE4481 [18] GSE24207 [73] GSE28621 [21] GSE11291 [60] GSE39391 [21] GSE6675 [8] GSE46211 [18] GSE16496 [102] GSE54056 [12] GSE32529 [224] GSE1986 [17] GSE1871 [12] GSE7309 [12] GSE27675 [14] GSE40156 [42] GSE32986 [18] GSE10246 [182] GSE17097 [20] GSE37431 [6] GSE11898 [9] GSE27713 [7] GSE25778 [6] GSE44101 [6] GSE19073 [6] GSE8682 [8] GSE7863 [16] GSE33156 [18] GSE27261 [8] GSE28559 [30] GSE25088 [24] GSE56777 [8] GSE59437 [30] GSE13044 [59] GSE25257 [6] GSE13807 [10] GSE5127 [18] GSE14243 [6] GSE21247 [60] GSE8960 [18] GSE25423 [10] GSE6676 [8] GSE41342 [26] GSE15872 [18] GSE10528 [6] GSE43381 [26] GSE34091 [8] GSE10912 [6] GSE33770 [8] GSE23200 [6] GSE27717 [11] GSE9338 [42] GSE42061 [12] GSE21861 [8] GSE11862 [6] GSE17553 [16] GSE52474 [154] GSE5861 [6] GSE17797 [19] GSE27568 [16] GSE10965 [8] GSE7598 [8] GSE20335 [8] GSE27451 [6] GSE21193 [10] GSE19091 [6] GSE31849 [18] GSE34723 [101] GSE23081 [6] GSE27378 [8] GSE38672 [6] GSE42047 [24] GSE7596 [6] GSE5333 [16] GSE5313 [6] GSE6487 [30] GSE13490 [15] GSE25244 [9] GSE34206 [8] GSE12498 [12] GSE46443 [12] GSE8621 [12] GSE34279 [30] GSE43779 [6] GSE9061 [6] GSE34618 [7] GSE16751 [6] GSE10290 [24] GSE41907 [7] GSE47421 [24] GSE51804 [10] GSE9038 [24] GSE43059 [8] GSE24695 [9] GSE21842 [8] GSE40377 [42] GSE18907 [12] GSE7838 [9] GSE30488 [52] GSE7275 [8] GSE5582 [6] GSE14004 [9] GSE46094 [10] GSE40282 [6] GSE29081 [6] GSE13402 [7] GSE28731 [10] CEM+ CEM GSE39442 [11] GSE9725 [16] GSE5891 [6] GSE33308 [10] GSE31150 [6] GSE30852 [6] 0.0 GSE44175 [18] GSE28457 [24]

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23895 Status: Public on Jan 19 2011 Title: Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21226930 Summary & Design: Summary: Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency.

Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 ´g Se/g diet.

Overall design: Rats or mice were fed Se-deficient diets supplemented with sodium selenite up to 5 ug Se/g diet for 28 or 35 days. Affymetrix Rat 230 2.0 and Mouse 430 2.0 Genome Arrays were used to analyze gene expression in liver in all studies plus kidney in the mouse study.

Background corr dist: KL-Divergence = 0.0133, L1-Distance = 0.0509, L2-Distance = 0.0031, Normal std = 0.9121

0.437 Kernel fit Pairwise Correlations Normal fit

Density 0.219

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

MouseLiver_SeDef_rep1MouseLiver_SeDef_rep2MouseLiver_SeDef_rep3MouseLiver_0.05ugSe_rep1 (0.0607443)MouseLiver_0.05ugSe_rep2 (0.0454568)MouseLiver_0.05ugSe_rep3 (0.0537683)MouseLiver_0.2ugSe_rep1 (0.0558941)MouseLiver_0.2ugSe_rep2 (0.0492972)MouseLiver_0.2ugSe_rep3 (0.0445979)MouseKidney_SeDef_rep1 (0.0600928)MouseKidney_SeDef_rep2 (0.0564216)MouseKidney_SeDef_rep3 (0.0465558)MouseKidney_0.05ugSe_rep1 (0.0332781)MouseKidney_0.05ugSe_rep2 (0.0388782)MouseKidney_0.05ugSe_rep3 (0.0263581)MouseKidney_0.2ugSe_rep1 MouseKidney_0.2ugSe_rep2(0.0664466) MouseKidney_0.2ugSe_rep3(0.0462797) (0.0560668) (0.13413) (0.0663758) (0.0593578)[ min ] [ medium ] [ max ] CEM 1 Arl6 188.7 1647.0 2239.9 P ( S | Z, I ) = 1.00 Ttc8 121.1 554.4 1168.8 Mean Corr = 0.94608 Bbs1 100.7 323.5 398.9 Bbs2 73.9 219.7 324.4 Bbs5 207.5 343.9 448.4 Bbs9 150.3 232.6 307.1 Bbs4 126.8 274.4 349.6 Wdr19 126.5 281.5 335.0 1110051M20Rik 301.0 595.1 774.9 Tmem237 78.2 1305.4 2000.6 Ttc26 88.8 282.3 343.6 Ift74 97.8 410.1 531.5 CEM 1 + Cep290 21.7 37.2 49.1 Top 10 Genes Fam229b 95.0 195.1 234.3 Dync2li1 173.7 846.0 1208.3 Ccdc104 623.6 1466.8 1804.6 Ift80 292.8 383.3 425.8

Null module Bbs7 Bbip1 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 "GSE29318" 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=GSE29318 Status: Public on Jul 12 2011 Title: Expression profile of FAC-sorted murine retinal cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21743009 Summary & Design: Summary: Microarray experiments were performed using FAC-sorted young photoreceptors to analyze their transcriptome in comparison to remaining retinal cells at same developmental stage and retinal progenitors.

Overall design: For each replicate, retinae of 6 to 8 postnatal day 0 pNestin-GFP or postnatal day 4 rhoEGFP mice were dissected and FAC-sorted based on GFP expression. RNA of fractions was isolated and subsequently analyzed with microarray experiment.

Background corr dist: KL-Divergence = 0.0360, L1-Distance = 0.0199, L2-Distance = 0.0006, Normal std = 0.6174

0.646 Kernel fit Pairwise Correlations Normal fit

Density 0.323

0.000 CEM 1

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

Pre-normalization Quantiles

rhoGFPrhoGFP PN4 retinalrhoGFP PN4 cellsretinalrhoGFP PN4 positive cellsretinalrhoGFP PN4 positive FAC cellsretinalrhoGFP PN4sorted positive FAC cellsretinalnestinGFP PN4biologicalsorted negative FAC cellsretinalnestinGFP biologicalsorted negative PN0 repliacte FACcellsnestinGFP retinalbiological sorted negative PN0 repliacteFAC 1 (0.272609) cellsretinal biologicalsorted PN0 repliacteFAC positive2 (0.159456) cellsretinal biologicalsorted repliacte positive3 FAC (0.149689)cells biological sortedrepliacte positive 1FAC [(0.0279606) min biological sortedrepliacte 2FAC (0.092639) biologicalsorted] 3repliacte (0.0759287) biological repliacte 1 (0.0702904)[ medium repliacte 2 (0.0732006) 3 (0.0782267) ] [ max ] CEM 1 Arl6 1520.8 2413.8 11871.2 P ( S | Z, I ) = 1.00 Ttc8 602.4 1202.1 3884.7 Mean Corr = 0.93804 Bbs1 712.6 894.2 2609.1 Bbs2 703.4 946.9 2068.0 Bbs5 555.3 826.4 4056.9 Bbs9 412.9 653.6 2112.4 Bbs4 142.9 195.1 630.1 Wdr19 418.9 494.9 957.1 1110051M20Rik 1149.6 1483.7 3433.7 Tmem237 536.6 898.9 3421.4 Ttc26 346.6 483.2 598.7 Ift74 969.5 1401.0 1731.2 CEM 1 + Cep290 223.2 398.2 1755.9 Top 10 Genes Fam229b 310.4 355.7 789.8 Dync2li1 972.4 1204.0 3052.1 Ccdc104 1034.4 1389.0 2568.7 Ift80 566.6 759.4 1212.3

Null module Bbs7 Bbip1 GEO Series "GSE9441" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: brain, genetic background, sleep deprivation

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

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

0.436 Kernel fit Pairwise Correlations Normal fit

Density 0.218

0.000 CEM 1

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

Pre-normalization Quantiles

B_AK_Control_ZTB_AK_Control_ZTB_AK_Control_ZT 6_1 B_AK_SleepDep_ZT(0.0305003) 6_2 B_AK_SleepDep_ZT(0.0302196) 6_3 B_AK_SleepDep_ZT(0.0334464) 6_1B_B6_Control_ZT (0.0265448) 6_2B_B6_Control_ZT (0.0266651) 6_3B_B6_Control_ZT (0.017068) 6_1 B_B6_SleepDep_ZT(0.0252543) 6_2 B_B6_SleepDep_ZT(0.023927) 6_3 B_B6_SleepDep_ZT(0.0216114) 6_1B_D2_Control_ZT (0.0243807) 6_2B_D2_Control_ZT (0.0337929) 6_3B_D2_Control_ZT (0.023486) 6_1 B_D2_SleepDep_ZT(0.0314368) 6_2 B_D2_SleepDep_ZT(0.021896) 6_3 B_D2_SleepDep_ZT(0.0313498) 6_1L_AK_Control_ZT (0.033242) 6_2L_AK_Control_ZT (0.0193332) 6_3L_AK_Control_ZT (0.0277254) 6_1 L_AK_SleepDep_ZT(0.0410519) 6_2 L_AK_SleepDep_ZT(0.0305765) 6_3 L_AK_SleepDep_ZT(0.0253325) 6_1L_B6_Control_ZT (0.0227697) 6_2L_B6_Control_ZT (0.0276932) 6_3L_B6_Control_ZT (0.0219593) 6_1 (0.0271779)L_B6_SleepDep_ZT 6_2 (0.0290103)L_B6_SleepDep_ZT 6_3 (0.0216588)L_B6_SleepDep_ZT 6_1L_D2_Control_ZT (0.0332765) 6_2L_D2_Control_ZT (0.0327607) 6_3L_D2_Control_ZT (0.0364981) 6_1 (0.0267269)L_D2_SleepDep_ZT 6_2 (0.0253562)L_D2_SleepDep_ZT 6_3 (0.0254358)L_D2_SleepDep_ZT 6_1 (0.0215483) 6_2 (0.0372632) 6_3 (0.0320248)[ min ] [ medium ] [ max ] CEM 1 Arl6 103.8 597.3 1129.9 P ( S | Z, I ) = 1.00 Ttc8 138.7 439.8 732.4 Mean Corr = 0.93531 Bbs1 46.8 312.9 435.5 Bbs2 79.8 337.0 621.8 Bbs5 123.2 438.7 639.9 Bbs9 102.5 163.5 227.4 Bbs4 39.3 84.6 116.5 Wdr19 76.1 284.9 360.9 1110051M20Rik 79.4 1648.3 2105.9 Tmem237 46.3 241.2 645.6 Ttc26 38.9 100.5 176.3 Ift74 76.3 372.9 661.7 CEM 1 + Cep290 32.2 50.4 93.4 Top 10 Genes Fam229b 51.9 206.2 339.4 Dync2li1 105.9 381.3 517.2 Ccdc104 717.5 2289.8 3197.9 Ift80 74.1 360.3 530.6

Null module Bbs7 Bbip1 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 (0.040272)mus-6dpp-50ng_activin-rep1 (0.0841556)mus-6dpp-50ng_activin-rep2 (0.0774989)mus-15dpp-0ng_activin-rep1 (0.0831492)mus-15dpp-0ng_activin-rep2 (0.102926)mus-15dpp-5ng_activin-rep1 (0.0782829)mus-15dpp-5ng_activin-rep2 (0.145961) (0.121008) (0.187426) (0.0793197)[ min ] [ medium ] [ max ] CEM 1 Arl6 528.9 774.0 1559.0 P ( S | Z, I ) = 1.00 Ttc8 473.3 625.6 816.2 Mean Corr = 0.91100 Bbs1 141.0 191.2 548.6 Bbs2 235.8 340.0 817.8 Bbs5 273.8 412.8 1058.8 Bbs9 200.8 342.8 518.7 Bbs4 63.7 121.6 184.4 Wdr19 207.3 334.2 770.5 1110051M20Rik 447.1 557.3 792.5 Tmem237 948.4 1050.0 1341.8 Ttc26 180.3 276.2 866.7 Ift74 1106.1 1322.1 3729.3 CEM 1 + Cep290 173.2 399.9 1311.4 Top 10 Genes Fam229b 151.4 234.7 3075.0 Dync2li1 956.5 1114.8 1545.7 Ccdc104 1025.9 1338.7 4811.5 Ift80 271.4 432.2 1526.9

Null module Bbs7 Bbip1 GEO Series "GSE31972" 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=GSE31972 Status: Public on Dec 07 2011 Title: Transcriptional profiling of ICAM-positive and -negative cells from the mouse olfactory epithelium Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: We used trasncriptional profiling of fluorescent activated cell sorting (FACS) purified ICAM1-positive and negative cells from the olfactory epithelium (OE) of three-week old mice to identify genes enriched in the horizontal basal cells.

Overall design: The olfactory epithelia from P21-P25 CD1 mice (Charles River Laboratories, Wilmington, MA), were isolated, dissociated, and then purified by FACS using a FITC-conjugated antibody for ICAM1 (CD54). ICAM1-positive and negative cell populations were collected and compared. RNA was purified with TRIzol reagent (Invitrogen, Carlsbad, CA), subjected to two rounds of amplification, labeled, and hybridized to Affymetrix Mouse Genome 430.2 GeneChip microarrays (Affymetrix Inc., Santa Clara, CA, USA) using Affymetrix reagents and protocols (http://www.affymetrix.com). There were three experimental replicates, each consisting of the ICAM1 (+) and ICAM1 (-) FACS purified cell populations from individual litters of mice that were dissected/dissociated/FACS-purified using an ICAM1-FITC conjugated antibody; one microarray was used for each ICAM1 (+) and ICAM1 (-) sample for a total of six microarrays. Microarray data were normalized using GCRMA.

Background corr dist: KL-Divergence = 0.0145, L1-Distance = 0.0398, L2-Distance = 0.0017, Normal std = 0.8821

0.490 Kernel fit Pairwise Correlations Normal fit

Density 0.245

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

Mm OE MmICAM1-negative-1 OE MmICAM1-positive-1 OE MmICAM1-negative-2 (0.216705)OE MmICAM1-positive-2 (0.167139) OE MmICAM1-negative-3 (0.157239)OE ICAM1-positive-3 (0.180514) (0.154278) (0.124125)[ min ] [ medium ] [ max ] CEM 1 Arl6 1086.0 5848.6 6608.4 P ( S | Z, I ) = 1.00 Ttc8 605.9 2544.7 3537.1 Mean Corr = 0.90429 Bbs1 488.8 2231.1 2829.3 Bbs2 520.5 808.0 916.2 Bbs5 285.9 972.4 1311.6 Bbs9 189.2 915.4 1072.1 Bbs4 36.6 81.9 115.8 Wdr19 453.7 1726.9 2077.6 1110051M20Rik 590.4 1714.1 2551.3 Tmem237 1515.0 1668.0 1856.8 Ttc26 240.7 823.9 1062.5 Ift74 418.4 864.6 2116.2 CEM 1 + Cep290 260.1 415.1 975.8 Top 10 Genes Fam229b 120.7 612.9 822.2 Dync2li1 1212.8 1989.3 2755.2 Ccdc104 609.2 2576.9 3701.5 Ift80 806.5 3155.2 3379.5

Null module Bbs7 Bbip1 GEO Series "GSE48338" 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=GSE48338 Status: Public on Jun 03 2014 Title: Tpl2 promotes chemokine/chemokine receptor expression and macrophage migration during acute inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24713702 Summary & Design: Summary: In autoimmune diseases, accumulation of activated leukocytes correlates with inflammation and disease progression, and therefore, disruption of leukocyte trafficking is an active area of research. The protein kinase Tpl2 (MAP3K8) regulates leukocyte inflammatory responses and is also being investigated for therapeutic inhibition during autoimmunity. Herein, we addressed the contribution of Tpl2 to the regulation of macrophage chemokine and chemokine receptor expression and subsequent migration in vivo using a mouse model of Tpl2 ablation. We found that gene expression of the chemokine ligands CCL2, CCL7, CXCL2, and CXCL3 as well as the chemokine receptors CCR1 and CCR5 were reduced in macrophages from the bone marrow and peritoneal cavities of tpl2-/- mice following stimulation with LPS. LPS stimulation repressed chemokine receptor expression of CCR1, CCR2 and CCR5. Notably, LPS-induced repression of CCR1 and CCR5 was significantly enhanced in Tpl2-deficient macrophages and was observed to be dependent upon Erk activation and independent of PI3K and mTOR signaling. Consistent with alterations in chemokine and chemokine receptor expression, tpl2-/- macrophages were defective in trafficking to the peritoneal cavity following thioglycollate-induced inflammation. Overall, this study demonstrates a Tpl2-dependent mechanism for macrophage expression of both chemokine receptors and their ligands and provides further insight into how Tpl2 inhibition may disrupt inflammatory networks in vivo.

Overall design: microarray was used to profile the genome-wide expression patterns in Tpl2 wild-type and deficient macrophage.

Background corr dist: KL-Divergence = 0.0154, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.8097

0.493 Kernel fit Pairwise Correlations Normal fit

Density 0.246

0.000 CEM 1

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

Pre-normalization Quantiles

BMDM, BMDM,Tpl2 WT, BMDM,Tpl2 unstimulated, WT, BMDM,Tpl2 unstimulated, KO, BMDM,Tpl2 biologicalunstimulated, KO, BMDM,Tpl2 biologicalunstimulated, replicate WT, BMDM,Tpl2 biological LPS replicate WT, 1treated, BMDM, Tpl2(0.128813) biological LPS replicate KO, 2treated, biologicalTpl2(0.153627) LPS replicate KO, 1treated, biological(0.105232) LPS replicate 2treated, biological(0.125531) replicate 1 (0.15991) biological[ minreplicate 2 (0.151309) replicate ]1 (0.106239) 2 (0.0693395)[ medium ] [ max ] CEM 1 Arl6 150.7 418.3 461.8 P ( S | Z, I ) = 1.00 Ttc8 71.5 196.1 284.0 Mean Corr = 0.88941 Bbs1 48.7 55.4 69.7 Bbs2 44.3 159.3 180.6 Bbs5 68.6 175.9 201.3 Bbs9 112.5 165.3 182.9 Bbs4 26.2 37.2 40.8 Wdr19 134.8 236.2 276.9 1110051M20Rik 277.8 497.0 540.0 Tmem237 467.2 625.2 798.3 Ttc26 40.9 56.5 64.3 Ift74 118.2 363.6 418.6 CEM 1 + Cep290 27.7 45.7 49.7 Top 10 Genes Fam229b 58.6 108.3 125.0 Dync2li1 213.5 252.4 324.3 Ccdc104 338.2 579.2 695.4 Ift80 73.9 136.6 193.2

Null module Bbs7 Bbip1 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(0.110009)testes biological(0.170431)testes at P21,rep2 at P21,biologicalrep2(0.17753) biological(0.148731) rep3[ rep3(0.255258)min (0.138041) ] [ medium ] [ max ] CEM 1 Arl6 1583.5 2104.1 2258.3 P ( S | Z, I ) = 1.00 Ttc8 665.1 1015.5 1116.0 Mean Corr = 0.87070 Bbs1 362.9 821.9 864.0 Bbs2 492.7 601.3 789.0 Bbs5 491.4 720.5 904.6 Bbs9 826.2 1064.3 1186.1 Bbs4 73.5 82.7 96.4 Wdr19 385.5 670.1 763.1 1110051M20Rik 730.3 1426.1 1621.4 Tmem237 843.0 1264.8 1459.8 Ttc26 710.9 1177.3 1257.8 Ift74 2277.0 5987.8 7007.0 CEM 1 + Cep290 812.7 1021.2 1181.0 Top 10 Genes Fam229b 1992.6 14689.9 15611.7 Dync2li1 1453.1 1981.1 2110.1 Ccdc104 2895.5 10891.0 11642.6 Ift80 917.8 2198.9 2507.9

Null module Bbs7 Bbip1 GEO Series "GSE22824" 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=GSE22824 Status: Public on Jan 01 2011 Title: Gene expression in retina and LGN of wild type and Chrnb2-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21547082 Summary & Design: Summary: Mice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.

Using microarray hybridization, we identified transcripts which are differentially expressed between Chrnb2-/- and wild type animals in these two tissues at these two ages.

Overall design: mRNA was isolated from retina and LGN of three male littermates each of WT and Chrnb2-/- mice at P4. mRNA from retinas of two adult male littermates of each type was also examined.

Background corr dist: KL-Divergence = 0.0272, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6813

0.595 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

PicciottoPicciotto b2 -/- Picciottoretina b2 -/- P4, Xuretina b2 mouseb2 -/- -/-P4, Xuretina retina Amouseb2 (0.00253462) -/-P4, XuP4, retina Bmouseb2 mouse (0.00602853) -/- WildP4, retina C Amouse (0.0111713)type (0.00742038) WildP4, retina Bmouse type (0.0112297)Wild P4, retina C typemouse (0.0196335)Picciotto P4, retina Amouse (0.0166191)Picciotto P4, b2 B-/-LGNmouse (0.00953377)Picciotto b2 P4,C-/- (0.0108348)XuLGN mouse b2 b2 -/-P4, -/- XuLGN BLGNmouse (0.0391541)b2 P4, -/-P4,Xu LGNCmouse mouse b2(0.0403165) -/-P4,Wild LGND Amouse (0.0336235) (0.0429391)type P4,Wild LGNBmouse (0.0433023)type WildP4, LGNC mouse (0.0406619)type PicciottoP4, LGN Amouse (0.0427992) PicciottoP4, b2 Dmouse -/- (0.0410966) Xuretina b2 b2E -/- (0.0442591)-/-adult, Xuretina retina b2 mouse -/-adult, Wildadult, retina type1542mouse mouse Wildadult, retina(0.138238) type1543 77mouse adult, (0.0744785) retina(0.0679266) 78 mouse adult,(0.0694118) 748mouse (0.0980593) 763[ min (0.0887272) ] [ medium ] [ max ] CEM 1 Arl6 1513.6 4976.6 7074.1 P ( S | Z, I ) = 1.00 Ttc8 273.8 1881.3 3616.3 Mean Corr = 0.86818 Bbs1 477.9 721.8 1798.3 Bbs2 181.5 632.4 1754.1 Bbs5 186.4 1216.1 3375.9 Bbs9 104.5 550.1 1334.6 Bbs4 103.7 646.4 1875.1 Wdr19 278.2 563.3 1298.6 1110051M20Rik 1765.7 2138.3 2484.8 Tmem237 780.1 977.0 2214.2 Ttc26 174.0 280.9 400.1 Ift74 404.1 1369.3 1868.9 CEM 1 + Cep290 28.0 375.4 978.9 Top 10 Genes Fam229b 413.5 558.0 727.2 Dync2li1 506.4 863.5 1503.1 Ccdc104 1576.2 2784.3 3235.3 Ift80 149.9 507.6 997.5

Null module Bbs7 Bbip1 GEO Series "GSE21900" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.784 Kernel fit Pairwise Correlations Normal fit

Density 0.392

0.000 CEM 1

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

Pre-normalization Quantiles

P1-control-ex1P1-control-ex2 P1-control-ex3(0.0139115) P1-Otx2-CKO-ex1(0.0249479) P1-Otx2-CKO-ex2(0.0309011)P1-Otx2-CKO-ex3 (0.0304574)P12-control-ex1 (0.0412007)P12-control-ex2 (0.0386089)P12-control-ex3 (0.253639)P12-Otx2-CKO-ex1 (0.193995)P12-Otx2-CKO-ex2 (0.228398)P12-Otx2-CKO-ex3 (0.0251729) (0.0385709) (0.0801961)[ min ] [ medium ] [ max ] CEM 1 Arl6 948.6 1497.6 6396.2 P ( S | Z, I ) = 1.00 Ttc8 700.5 1270.9 5100.8 Mean Corr = 0.84688 Bbs1 409.8 621.1 2878.2 Bbs2 301.3 387.0 937.9 Bbs5 214.0 469.5 3216.5 Bbs9 217.6 365.3 1856.4 Bbs4 56.2 118.6 342.3 Wdr19 305.4 433.4 815.8 1110051M20Rik 878.3 1325.0 4322.0 Tmem237 908.1 1186.1 4107.7 Ttc26 118.5 285.8 342.1 Ift74 108.9 777.5 1648.8 CEM 1 + Cep290 44.1 185.0 1637.3 Top 10 Genes Fam229b 186.7 429.0 1086.0 Dync2li1 402.0 969.8 1904.7 Ccdc104 853.3 1619.9 2162.2 Ift80 173.0 621.1 916.4

Null module Bbs7 Bbip1 GEO Series "GSE6540" 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=GSE6540 Status: Public on Dec 14 2007 Title: Expression data from olfactory epithelium of Lip-C-treated mice compared to Lip-O-treated control mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17848607 Summary & Design: Summary: Microarray analysis of gene expression in the olfactory epithelium of macrophage depleted mice to study the role of macrophages in regulating neurodegeneration, neuroprotection, and neurogenesis of olfactory sensory neurons

Keywords: comparison of gene expression level in sham and 48 hr OBX Lip-O mice versus Lip-C mice

Overall design: Olfactory epithelium from LIp-C-treated and Lip-O-treated mice was microdissected for RNA extraction and hybridization on Affymetrix microarrays. We compared levels of gene expression in macrophage-depleted and non-depleted sham and 48 hr OBX mice using a 2x2 ANOVA and pairwise comparisons to identify molecular mechanisms of macrophage-mediated neurodegeneration, neuroprotection, and neurogenesis and to validate the gene expression patterns using real-time RT-PCR and immunohistochemistry

Background corr dist: KL-Divergence = 0.1195, L1-Distance = 0.0264, L2-Distance = 0.0010, Normal std = 0.4100

0.973 Kernel fit Pairwise Correlations Normal fit

Density 0.487

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

Lip-C-treatedLip-C-treated 48Lip-C-treated hr OBX 48Lip-C-treated hrC57 OBX 48mouse,Lip-C-treated hrC57 OBX sham mouse,biolLip-C-treated C57 rep1 OBX sham mouse,biolLip-O-treated (0.0918139) C57 rep2 OBX sham mouse,biolLip-O-treated (0.0490603) C57 rep3 OBX 48 mouse,Lip-O-treatedbiol (0.0195332)hr C57 rep1OBX 48 mouse,Lip-O-treatedbiol hr(0.0655508)C57 rep2OBX 48mouse, Lip-O-treatedbiol hr(0.121442)C57 rep3OBX sham mouse,biolLip-O-treated (0.0779803)C57 rep1 OBX sham mouse,biol (0.149476) C57 rep2 OBX sham mouse,biol (0.129042) C57 rep3 OBX mouse,biol (0.0898342) C57 rep1 mouse,[biol (0.107571)min rep2 biol (0.0544109) rep3] (0.0442855)[ medium ] [ max ] CEM 1 Arl6 2418.5 3644.4 4114.9 P ( S | Z, I ) = 1.00 Ttc8 1401.4 2451.3 2677.7 Mean Corr = 0.82047 Bbs1 655.8 1062.9 1377.7 Bbs2 628.0 1069.9 1380.3 Bbs5 916.3 1439.7 1828.6 Bbs9 605.6 781.2 910.3 Bbs4 84.4 121.6 138.6 Wdr19 773.5 1253.2 1718.5 1110051M20Rik 908.5 1328.4 1515.6 Tmem237 1424.3 1540.3 1766.8 Ttc26 638.0 973.5 1122.9 Ift74 2290.2 3039.5 3784.1 CEM 1 + Cep290 434.4 767.8 892.3 Top 10 Genes Fam229b 485.0 740.3 946.1 Dync2li1 1781.4 1941.7 2258.2 Ccdc104 3477.9 4959.1 6113.3 Ift80 1212.0 2087.6 2578.2

Null module Bbs7 Bbip1 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,(0.0689674) 1 type (0.0648834) sample,mice, replica brainVastusmice, replica wild biological tissue wild2biological muscletypeLateralis,(0.0511826) 2 type (0.035205) sample,mice, replica brainVastusmice, replica mutant biological tissue mutant3biological muscleLateralis,(0.0757135) 3 mice, (0.0554443) sample, mice,replica brainVastus biological replica mutant biological tissue mutant4 Lateralis,(0.096726) 4 mice, (0.0842275) replicasample, mice, replica biological mutant 1biological mutant(0.0612292) 1 (0.106073) mice, replica mice, replica[ biological min 2biological (0.0509949) 2 (0.0789679) replica] replica 3 (0.0754064) 3 (0.0949787)[ medium ] [ max ] CEM 1 Arl6 160.3 994.1 1595.1 P ( S | Z, I ) = 1.00 Ttc8 203.1 621.3 787.8 Mean Corr = 0.80916 Bbs1 41.3 442.3 545.8 Bbs2 62.6 247.6 359.7 Bbs5 112.3 381.3 533.1 Bbs9 125.9 153.8 203.7 Bbs4 106.1 164.5 269.3 Wdr19 142.3 350.5 432.7 1110051M20Rik 411.5 1270.2 1802.2 Tmem237 335.2 606.3 1033.8 Ttc26 109.0 219.0 299.3 Ift74 358.6 575.0 1061.9 CEM 1 + Cep290 74.7 161.2 249.3 Top 10 Genes Fam229b 145.6 313.8 404.7 Dync2li1 481.5 740.8 917.5 Ccdc104 659.6 2360.9 3245.3 Ift80 112.6 359.5 564.5

Null module Bbs7 Bbip1 GEO Series "GSE24512" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 29 -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=GSE24512 Status: Public on Mar 15 2012 Title: Expression variation in the mouse retina Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21779340 Summary & Design: Summary: Expression analysis of multiple mouse strains across two developmental timepoints to determine both strain specific and temporal expression of genes in the mouse retina

Overall design: A total of 29 retinas were collected from 15 mice of each strain at similar time points during the day. Equimolar amounts of RNA isolated from ten retinas were pooled into three separate pools from each strain and time point, then hybridized to Affymetrix Mouse 420A 2.0 GeneChip arrays.

Background corr dist: KL-Divergence = 0.1455, L1-Distance = 0.0524, L2-Distance = 0.0048, Normal std = 0.3969

1.073 Kernel fit Pairwise Correlations Normal fit

Density 0.536

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

C57BL6/JC57BL6/J P30.5C57BL6/J 5-3-07 P30.5C57BL6/J (0.0255395) 4-12-07 P30.5C57BL6/J 4-19-07(0.0748074) E18.5C57BL6/J 5-3-07(0.0164224) E18.5RD7 (0.0196406) 4-19-07 E18.5 P30.5RD7 4-20-07(0.0226653) 5-3-07 P30.5RD7 (0.0171073) (0.0371278) 4-12-07 P30.5RD7 4-19-07(0.077692) E18.5RD7 5-3-07(0.0226211) E18.5RD7 (0.0280731) 4-12-07 E18.5AKR/J 4-19-07(0.0277351) P30.5AKR/J (0.0275411) 5-3-07 P30.5AKR/J (0.0182797) 14 P30.5AKR/J 4-19-07 15 E18.5AKR/J 4-19-07(0.0184243) 5-3-07 E18.5NOD.NON-H2-NB1 (0.0159509) (0.0328042) 4-19-07NOD.NON-H2-NB1 (0.0358509)NOD.NON-H2-NB1 P30.5NOD.NON-H2-NB1 5-3-07 P30.5NOD.NON-H2-NB1 (0.0323809) 4-12-07 P30.5NOD.NON-H2-NB1 4-19-07(0.0658825) E18.5CAST/EiJ 5-3-07(0.0325108) E18.5CAST/EiJ (0.0259861) 4-12-07P30.5 E18.5CAST/EiJ 5-3-07 4-19-07P30.5(0.0288152) CAST/EiJ(0.0566859) 4-12-07 P30.5(0.0227025)CAST/EiJ 4-19-07(0.0651496) E18.5CAST/EiJ 5-3-07(0.0437625) E18.5 (0.0403625) 4-12-07 E18.5 4-19-07(0.0323572) (0.0351216)[ min ] [ medium ] [ max ] CEM 1 Arl6 2007.0 6111.3 14029.8 P ( S | Z, I ) = 1.00 Ttc8 847.3 3577.3 5682.8 Mean Corr = 0.80151 Bbs1 542.5 1270.8 2660.7 Bbs2 238.2 1100.5 1945.2 Bbs5 291.4 1955.0 4886.5 Bbs9 211.0 985.6 2294.0 Bbs4 48.3 102.9 287.1 Wdr19 342.7 609.0 898.6 1110051M20Rik 830.0 1332.0 2228.3 Tmem237 849.2 3772.1 6726.0 Ttc26 161.1 313.4 411.5 Ift74 663.2 1107.3 2054.5 CEM 1 + Cep290 318.0 1705.0 3849.3 Top 10 Genes Fam229b 186.9 345.3 735.9 Dync2li1 801.7 1111.6 1353.5 Ccdc104 1265.3 2023.9 3710.0 Ift80 687.7 1257.7 1643.4

Null module Bbs7 Bbip1 GEO Series "GSE27605" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.614 Kernel fit Pairwise Correlations Normal fit

Density 0.307

0.000 CEM 1

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

Pre-normalization Quantiles

intestine-Lgr5High-R1intestine-Lgr5Low-R1intestine-EphB2High-R1 intestine-EphB2Medium-R1(0.172853) (0.0381027)intestine-EphB2Low-R1intestine-EphB2High-R2 (0.136437)intestine-EphB2Medium-R2 (0.0192183)intestine-EphB2Low-R2 (0.156996) (0.185678) (0.015728) (0.274987)[ min ] [ medium ] [ max ] CEM 1 Arl6 32.7 63.3 106.8 P ( S | Z, I ) = 1.00 Ttc8 9.5 21.2 31.0 Mean Corr = 0.80044 Bbs1 17.7 32.2 61.0 Bbs2 343.5 576.4 738.7 Bbs5 99.7 391.7 463.3 Bbs9 92.1 153.2 280.6 Bbs4 81.5 165.8 210.2 Wdr19 66.0 166.1 236.1 1110051M20Rik 88.3 222.4 505.8 Tmem237 73.3 182.8 279.3 Ttc26 12.8 49.7 83.1 Ift74 198.8 337.9 522.4 CEM 1 + Cep290 77.9 112.0 143.9 Top 10 Genes Fam229b 10.9 60.3 118.5 Dync2li1 34.8 92.1 203.1 Ccdc104 113.0 291.4 417.2 Ift80 102.5 300.2 474.2

Null module Bbs7 Bbip1 GEO Series "GSE36833" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 49 -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=GSE36833 Status: Public on Mar 28 2012 Title: Gene Expression profiling in DBA/2J glaucoma Organism: Mus musculus Experiment type: Third-party reanalysis Platform: GPL1261 Pubmed ID: 22426214 Summary & Design: Summary: Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. Genome-wide assessment of gene expression changes was performed in DBA/2J-Gpnmb+, DBA/2J mice and irradiated DBA/2J mice at 8.5 and 10.5 months of age.

Overall design: In this study (Howell et al, JCI, 2012), 50 samples (10 D2-Gpnmb+ control at 8.5 mos, 20 NOE DBA/2J at 8.5 mos, 10 radiation-treated DBA2J at 8.5 mos and 10 radiation-treated DBA/2J at 10.5 mos) were combined with 30 of ONH samples from the GSE26299 study (10 D2-Gpnmb+ and 20 NOE DBA/2J all at 10.5 mos). One D2-Gpnmb+ 8.5mo sample failed QC and was not included in the analysis. Quantile normalization was performed for all optic nerve head samples reported in the study. The complete dataset is linked below as a supplementary file.

Background corr dist: KL-Divergence = 0.4034, L1-Distance = 0.0737, L2-Distance = 0.0161, Normal std = 0.2470

1.615 Kernel fit Pairwise Correlations Normal fit

Density 0.808

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

Rad-D2 Rad-D2rep C4.7 Rad-D2rep (ONH) C3.6 D2-Gp2rep (0.026922) (ONH) C4.3D2-Gp1 rep(0.00677335) (ONH) B1.5Rad-D2 rep(0.00913834) (ONH) B6 Rad-D2(ONH)rep (0.0223016) C5.5 (0.019246) Stg1Arep (ONH) C5.10 repStg1A (0.0176438) B2.1(ONH) repStg1A (ONH) (0.0134095) B2.2 rep (0.0212009)Stg1B (ONH) B3.1 rep (0.0232469)Stg1B (ONH) B2.3 rep (0.00635771)Stg1B (ONH) B2.4 rep (0.017484)Stg1C (ONH) B3.2 rep (0.00298929)Stg1B (ONH) B3.4 rep (0.0041926)Rad-D2 (ONH) B2.9 (0.0299525) Rad-D2rep(ONH) C3.10 (0.0109929) Stg1Brep (ONH) C4.9 repRad-D2 (ONH)(0.0124599) B2.10 D2-Gp2rep (0.00786752) (ONH) C3.4D2-Gp2 rep(0.0296179) (ONH) B1.2D2-Gp2 rep(0.00429206) (ONH) B1.3D2-Gp2 rep (0.00684294) (ONH) B1.4D2-Gp1 rep (0.0213123) (ONH) B1.7Rad-D2 rep (0.014367) (ONH) B10 Rad-D2rep (0.0247514)(ONH) C5.4 Stg1Brep(0.0147522) (ONH) C5.9 repStg1B (0.00941125) (ONH) B2.5 repStg1B (ONH)(0.0452916) B2.6 rep (0.00701429)Stg1C (ONH) B3.5 rep (0.0336877)Stg1C (ONH) B3.6 rep (0.0364463)Stg1A (ONH) B3.9 rep (0.00536316)No_cluster (ONH) B3.10 (0.0178713)No_cluster (ONH) repNo_cluster C4.5(0.0529106) rep (ONH)No_cluster C3.2 rep (0.0604724) (ONH)No_cluster B1.1 rep (0.0170462) (ONH)No_cluster C5.1 rep (0.00808267) (ONH)No_cluster C5.2 rep (0.00428591) (ONH)No_cluster C5.6 rep (0.0270844) (ONH)No_cluster C5.7 rep (0.0456918) (ONH)No_cluster B2.7 rep (0.117247) (ONH)No_cluster B3.7 rep (0.0244072) (ONH)No_cluster C3.8 rep (0.00657125) (ONH)No_cluster B1.8 rep (0.00892161) (ONH)No_cluster C5.3 rep (0.0141199) (ONH)No_cluster C5.8 rep (0.0134341) (ONH)No_cluster B3.3 rep (0.0133762) (ONH)No_cluster B2.8 rep (0.00205503) (ONH) B3.8 rep (0.0213958) (ONH) C4.1 (0.00559533) (ONH) (0.0341023)[ min ] [ medium ] [ max ] CEM 1 Arl6 979.0 2134.1 3868.1 P ( S | Z, I ) = 1.00 Ttc8 341.8 601.0 1081.2 Mean Corr = 0.79269 Bbs1 425.5 606.0 1156.4 Bbs2 689.5 1063.7 1657.3 Bbs5 1328.6 2704.5 4470.0 Bbs9 144.0 299.7 577.8 Bbs4 294.1 481.0 822.7 Wdr19 537.2 717.0 984.5 1110051M20Rik 681.4 994.6 1251.9 Tmem237 317.6 468.8 775.1 Ttc26 64.0 116.7 203.7 Ift74 440.8 623.4 870.6 CEM 1 + Cep290 265.7 437.5 808.8 Top 10 Genes Fam229b 199.6 289.1 373.5 Dync2li1 429.4 530.2 744.7 Ccdc104 883.4 1156.9 1431.9 Ift80 2070.0 2644.8 3486.5

Null module Bbs7 Bbip1 GEO Series "GSE24813" 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=GSE24813 Status: Public on Aug 24 2011 Title: Gene expression data of BCR-ABL1 transformed myeloid cells from BCL6 wild-type and BCL6 knockout mice treated with and without Imatinib and RI-BPI Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21911423 Summary & Design: Summary: To identify differences in the gene regulation between BCL6+/+ and BCL6-/- CML cells a gene expression analysis has been performed. We investigated the gene expression pattern in BCL6+/+ cells in the presence or absence of Imatinib and a combination of Imatinib and RI-BPI (a novel retro-inverso BCL6 peptide inhibitor). In BCL6-/- CML cells, we investigated the gene expression pattern in the presence or absence of Imatinib.

Overall design: BCR-ABL1 transformed myeloid cells from BCL6+/+ mice were cultured in the presence or absence of 10´M Imatinib or 10´M Imatinib and 20´M RI-BPI for 16 hours. BCR-ABL1 transformed myeloid cells from BCL6-/- mice were cultured in the presence or absence of 10´M Imatinib. Two samples for each condition were processed.

Background corr dist: KL-Divergence = 0.0654, L1-Distance = 0.0414, L2-Distance = 0.0023, Normal std = 0.5423

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

BCL6 WTBCL6 chip WT 1BCL6 untreated chip WT 2BCL6 untreated chip (0.10457) WT 1BCL6 Imatinib chip (0.0804223) WT 2BCL6 Imatinib chiptreated WT 1BCL6 Imatinib/RI-BPI chiptreated(0.105456) KO 2BCL6 Imatinib/RI-BPI chip (0.128261) KO 1BCL6 untreated chiptreated KO 2BCL6 untreated chiptreated(0.0697766) (0.134335) KO 1 Imatinib chip(0.0990391) (0.110471) 2 Imatinib treated treated(0.0706015)[ min(0.0970675) ] [ medium ] [ max ] CEM 1 Arl6 157.2 287.0 427.9 P ( S | Z, I ) = 1.00 Ttc8 24.1 238.8 501.6 Mean Corr = 0.78492 Bbs1 40.0 57.8 96.1 Bbs2 138.7 563.3 742.1 Bbs5 76.4 181.3 280.2 Bbs9 300.2 475.5 572.6 Bbs4 73.6 128.4 142.4 Wdr19 94.8 263.0 394.5 1110051M20Rik 500.0 818.3 899.3 Tmem237 546.2 1049.4 1950.7 Ttc26 41.7 86.0 104.1 Ift74 473.3 742.8 1229.0 CEM 1 + Cep290 172.6 332.9 435.7 Top 10 Genes Fam229b 46.0 106.1 166.2 Dync2li1 50.0 65.9 130.5 Ccdc104 1311.3 1901.7 2703.5 Ift80 276.2 541.5 680.9

Null module Bbs7 Bbip1 GEO Series "GSE21568" 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=GSE21568 Status: Public on Jan 12 2011 Title: Mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21206086 Summary & Design: Summary: Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray

To compare the gene expression of mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+)

Bald scalp retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

Androgenetic alopecia (AGA) or common baldness results from a marked decrease in hair follicle size. This miniaturization may be related to loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from the same individuals for the presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing CYTOKERATIN 15 (KRT15), CD200, CD34 and ALPHA-6-INTEGRIN (ITGA6). High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. Consistent with a progenitor cell phenotype, the diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. In functional assays, analogous CD200 high /Itga6 high cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings suggest that a defect in stem cell activation plays a role in the pathogenesis of AGA.

Overall design: 4 independent biologic replicates (each pooled from 3 distinct mice) were sorted for Mouse bulge (CD34+CD200+CD49+) versus secondary hair germ (CD34-CD200+CD49+) versus interfollicular epidermis (CD34-CD200-CD49+)

Background corr dist: KL-Divergence = 0.0683, L1-Distance = 0.0257, L2-Distance = 0.0012, Normal std = 0.5061

0.788 Kernel fit Pairwise Correlations Normal fit

Density 0.394

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

CD34+CD200+CD49+Replicate1CD34+CD200+CD49+Replicate2CD34+CD200+CD49+Replicate3CD34+CD200+CD49+Replicate4CD34-CD200+CD49+Replicate1 (0.350945)CD34-CD200+CD49+Replicate2 (0.073784)CD34-CD200+CD49+Replicate3 (0.0487675)CD34-CD200+CD49+Replicate4 (0.128445)CD34-CD200-CD49+Replicate1 (0.040465)CD34-CD200-CD49+Replicate2 (0.0612941)CD34-CD200-CD49+Replicate3 (0.0910883)CD34-CD200-CD49+Replicate4 (0.0548655) (0.0231212) (0.020759) (0.0705023)[ (0.0359621) min ] [ medium ] [ max ] CEM 1 Arl6 352.1 435.3 615.7 P ( S | Z, I ) = 1.00 Ttc8 279.9 435.7 621.9 Mean Corr = 0.78192 Bbs1 120.8 175.6 390.7 Bbs2 515.0 1046.3 1745.6 Bbs5 286.8 343.6 682.1 Bbs9 175.2 293.9 621.2 Bbs4 377.1 549.2 878.3 Wdr19 300.1 334.4 595.9 1110051M20Rik 711.4 1252.4 1553.7 Tmem237 263.7 371.6 624.5 Ttc26 64.1 133.0 297.3 Ift74 668.5 1022.8 1576.1 CEM 1 + Cep290 225.8 271.7 347.4 Top 10 Genes Fam229b 90.4 136.8 425.3 Dync2li1 210.7 337.7 832.0 Ccdc104 297.9 429.5 783.1 Ift80 857.9 1682.7 2400.6

Null module Bbs7 Bbip1 GEO Series "GSE16675" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 72 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

Keywords: comparative genomic

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

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

0.711 Kernel fit Pairwise Correlations Normal fit

Density 0.356

0.000 CEM 1

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

Pre-normalization Quantiles

129_E14.5_brain_rep1129_E14.5_brain_rep2129_E14.5_brain_rep3 B6_E14.5_brain_rep1(0.0115197) B6_E14.5_brain_rep2(0.0146312) B6_E14.5_brain_rep3(0.0271685) (0.0215495)D2_E14.5_brain_rep1 (0.00927739)D2_E14.5_brain_rep2 (0.0237738)D2_E14.5_brain_rep3 (0.014434)129_E14.5_liver_rep1 (0.0176547)129_E14.5_liver_rep2 (0.0161544)129_E14.5_liver_rep3 (0.0136049)B6_E14.5_liver_rep1 (0.0158145)B6_E14.5_liver_rep2 (0.0123375)B6_E14.5_liver_rep3 (0.0201292)D2_E14.5_liver_rep1 (0.0184448)D2_E14.5_liver_rep2 (0.0176774)D2_E14.5_liver_rep3 (0.0118737)129_P1_brain_rep1 (0.00989233)129_P1_brain_rep2 (0.0115614)129_P1_brain_rep3 (0.00723981)B6_P1_brain_rep1 (0.00971006)B6_P1_brain_rep2 (0.00604137)B6_P1_brain_rep3 (0.00655098)D2_P1_brain_rep1 (0.00778273)D2_P1_brain_rep2 (0.00326735)D2_P1_brain_rep3 (0.00871285)129_P1_liver_rep1 (0.00747412)129_P1_liver_rep2 (0.00693476)129_P1_liver_rep3 (0.00929657)B6_P1_liver_rep1 (0.0126012)B6_P1_liver_rep2 (0.011322)B6_P1_liver_rep3 (0.00916859)D2_P1_liver_rep1 (0.0115227)D2_P1_liver_rep2 (0.0118383)D2_P1_liver_rep3 (0.0147182)129_P7_brain_rep1 (0.0122694)129_P7_brain_rep2 (0.0104205)129_P7_brain_rep3 (0.0141733)B6_P7_brain_rep1 (0.00640067)B6_P7_brain_rep2 (0.0118085)B6_P7_brain_rep3 (0.00867191)D2_P7_brain_rep1 (0.00577761)D2_P7_brain_rep2 (0.00647757)D2_P7_brain_rep3 (0.0167363)129_P7_liver_rep1 (0.00716046)129_P7_liver_rep2 (0.00757612)129_P7_liver_rep3 (0.00781352)B6_P7_liver_rep1 (0.00999692)B6_P7_liver_rep2 (0.00747671)B6_P7_liver_rep3 (0.00930824)D2_P7_liver_rep1 (0.0078539)D2_P7_liver_rep2 (0.00712588)D2_P7_liver_rep3 (0.0125818)129_P90_brain_rep1 (0.00878346)129_P90_brain_rep2 (0.00769578)129_P90_brain_rep3 (0.018197)B6_P90_brain_rep1 (0.0193046)B6_P90_brain_rep2 (0.0206468)B6_P90_brain_rep3 (0.0186366)D2_P90_brain_rep1 (0.0195333)D2_P90_brain_rep2 (0.0211004)D2_P90_brain_rep3 (0.0236817)129_P90_liver_rep1 (0.0199553)129_P90_liver_rep2 (0.025024)129_P90_liver_rep3 (0.0198317)B6_P90_liver_rep1 (0.0240288)B6_P90_liver_rep2 (0.0201066)B6_P90_liver_rep3 (0.0204961)D2_P90_liver_rep1 (0.0280867)D2_P90_liver_rep2 (0.0235592)D2_P90_liver_rep3 (0.0219797) (0.0187214) (0.0193208)[ min ] [ medium ] [ max ] CEM 1 Arl6 98.3 977.6 1790.7 P ( S | Z, I ) = 1.00 Ttc8 114.7 411.1 897.7 Mean Corr = 0.76722 Bbs1 37.8 439.8 720.0 Bbs2 65.6 315.4 616.0 Bbs5 100.5 246.6 653.5 Bbs9 89.8 168.2 243.0 Bbs4 61.6 123.2 274.5 Wdr19 72.0 270.0 423.5 1110051M20Rik 165.5 1369.6 1977.3 Tmem237 108.4 497.3 1317.8 Ttc26 42.2 185.1 397.3 Ift74 112.7 424.0 942.1 CEM 1 + Cep290 28.0 92.8 351.3 Top 10 Genes Fam229b 50.9 310.1 656.8 Dync2li1 106.3 651.5 1283.4 Ccdc104 360.9 1557.8 3385.0 Ift80 114.9 351.9 700.7

Null module Bbs7 Bbip1 GEO Series "GSE47196" 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=GSE47196 Status: Public on May 23 2013 Title: Immunoglobulin-like domain receptor 1 mediates fat-stimulated cholecystokinin secretion. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23863714 Summary & Design: Summary: Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild type but not ILDR1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation is associated with increased [Ca2+]i consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.

Overall design: GFP positive cells from CCK-EGFP transgenic mice were isolated by FACS and the expression profile was compared with an equal number of non-fluorescent intestinal cells.

Background corr dist: KL-Divergence = 0.0167, L1-Distance = 0.0318, L2-Distance = 0.0015, Normal std = 0.7899

0.505 Kernel fit Pairwise Correlations Normal fit

Density 0.253

0.000 CEM 1

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

Pre-normalization Quantiles

IntestinalIntestinal CCK-EGFPIntestinal non-EGFP cellsIntestinal CCK-EGFP rep1 cellsIntestinal (0.208627)non-EGFP rep1 cellsIntestinal (0.120323) non-EGFP rep2 cells (0.193928)CCK-EGFP rep2 cells (0.262957) rep3 cells (0.127076) rep3[ (0.0870891)min ] [ medium ] [ max ] CEM 1 Arl6 10.8 167.2 305.7 P ( S | Z, I ) = 1.00 Ttc8 11.9 171.2 297.0 Mean Corr = 0.74855 Bbs1 10.8 120.4 139.7 Bbs2 332.5 992.0 1273.0 Bbs5 21.3 181.0 380.6 Bbs9 29.4 109.3 335.1 Bbs4 94.2 286.8 329.8 Wdr19 12.9 227.0 296.8 1110051M20Rik 32.7 762.1 951.8 Tmem237 325.3 535.0 683.7 Ttc26 17.3 76.8 165.6 Ift74 98.0 405.9 630.4 CEM 1 + Cep290 38.1 172.5 808.1 Top 10 Genes Fam229b 9.1 168.4 234.0 Dync2li1 56.1 408.6 831.9 Ccdc104 30.9 370.9 623.7 Ift80 143.6 568.1 738.6

Null module Bbs7 Bbip1 GEO Series "GSE27630" 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=GSE27630 Status: Public on Feb 05 2013 Title: The transcription factor Otx2 regulates choroid plexus development and function Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23364326 Summary & Design: Summary: The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.

Overall design: We performed gene expression microarray analysis of fourth ventricular choroid plexus tissue from Otx2 k.o. mice compared to wildtype mice from the same litters.

Background corr dist: KL-Divergence = 0.0475, L1-Distance = 0.0207, L2-Distance = 0.0005, Normal std = 0.5785

0.695 Kernel fit Pairwise Correlations Normal fit

Density 0.348

0.000 CEM 1

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

Pre-normalization Quantiles

Fourth ventricularFourth ventricularFourth choroid ventricularFourth choroid plexus ventricularFourth choroid fromplexus ventricularFourth Otx2ko choroid fromplexus ventricularFourth Otx2komice choroid fromplexus ventricular Fourthat Otx2ko miceE13, choroid fromplexus ventricularbiologicalat Otx2ko miceE13, choroid fromplexus biologicalat wildtype mice E13, replicatechoroid fromplexus biologicalat wildtype E13, replicatemice from plexus1 (0.223456) [biological atwildtype min replicate miceE13,from 2 (0.110093) biologicalatwildtype replicate miceE13, ]3 (0.126009) biologicalat mice E13, replicate4 (0.0821335) biologicalat[ E13, replicatemedium 1 (0.0829433) biological replicate 2 (0.0908655) replicate 3 (0.109004)] 4 (0.175496)[ max ] CEM 1 Arl6 3500.6 5879.9 6761.4 P ( S | Z, I ) = 1.00 Ttc8 815.3 1148.8 1204.1 Mean Corr = 0.74515 Bbs1 694.9 1312.3 1441.1 Bbs2 498.1 787.0 838.1 Bbs5 616.4 1125.4 1261.7 Bbs9 313.1 519.9 546.1 Bbs4 87.4 99.9 107.1 Wdr19 649.9 885.0 1002.3 1110051M20Rik 1042.4 1175.5 1203.9 Tmem237 1304.6 2467.2 2524.7 Ttc26 472.6 696.2 796.0 Ift74 2264.1 3056.2 3419.0 CEM 1 + Cep290 129.2 190.9 230.7 Top 10 Genes Fam229b 483.6 597.1 740.1 Dync2li1 2768.3 3799.3 4263.2 Ccdc104 3206.5 5008.5 5915.3 Ift80 1147.5 1833.4 1995.0

Null module Bbs7 Bbip1 GEO Series "GSE40087" 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=GSE40087 Status: Public on Nov 13 2012 Title: Expression data from Middle Ear Mucosal Metaplasia in Mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Chronic Otitis Media (OM) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Non-typeable Haemophilus influenzae (NTHi), the most common acute OM pathogen, is known to activate inflammation and mucin expression in vitro and in animal models of OM. The goals of this study were to: examine expression profiling epithelial effects of NTHi challenge in murine middle ears.

We used microarrays to detail examine the global programme of gene expression underlying epithelial effects of NTHi challenge in murine middle ears during this study.

Overall design: Weekly transtympanic inoculation of Balb/c mice with 300 ´g/ml of NTHi lysates vs saline was performed. Bacteria were grown on chocolate agar at 37ÂºC in 5% CO2 overnight and inoculated in brain heart infusion (BHI) broth supplemented with 3.5 mg of nicotinamide adenine dinucleotide per ml. After overnight incubation, bacteria were subcultured into 5 ml of fresh brain heart infusion (BHI) and upon reaching log phase growth, NTHi were washed and suspended in phosphate-buffered saline (PBS) followed by sonication for lysis. Three transtympanic inoculation of 6 Balb/c mice middle ears (3 animals, 6 ears) with 50 uL of 300 ug/ml of NTHi bacterial lysate and 6 Balb/c mice middle ears (3 animals, 6 ears) with 50 uL of 1X phosphate buffered saline (PBS) were carried out weekly over 4 weeks (injection on days 7, 14, and 21). On day 28, the mice were euthanized and their bullae harvested. Expression microarray analysis was performed at 1 and 7 days. Microarray findings were validated in independent animal samples and in a cultured murine middle ear epithelial cell (mMEEC) line.

Background corr dist: KL-Divergence = 0.0855, L1-Distance = 0.0361, L2-Distance = 0.0025, Normal std = 0.4640

0.860 Kernel fit Pairwise Correlations Normal fit

Density 0.430

0.000 CEM 1

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

Pre-normalization Quantiles

S1 - salineS2 -treated salineS3 -treatedmouse, salineN1 -treated mouse, day1,NTHiN2 treated bio - mouse, dayNTHi rep1N3 1, treated mouse,-bio (0.0570723)dayNTHi rep2N4 1, treated mouse,-daybio NTHi(0.0475614) rep3N51, biotreated mouse,-day NTHi(0.0225508) rep1 N61, biotreated mouse, -day(0.0818201) NTHi rep2 WT11, biotreated mouse, day(0.019199) - rep3untreated WT27, bio mouse, day(0.0180427) - rep1untreated WT37, mouse, bio day(0.0636446) - rep2untreated S47, mouse,bio -(0.14156) saline reprep3S5 mouse,bio1 - treated(0.0708649) (0.0135965)saline repS6 bio2 - treatedmouse, (0.0570105)saline rep 3 treatedmouse,(0.0515079)day7, bio mouse,day7, rep1 bio (0.193925)day7, rep2[ biomin (0.0946924) rep3 (0.0669518)] [ medium ] [ max ] CEM 1 Arl6 1956.3 3230.6 4451.0 P ( S | Z, I ) = 1.00 Ttc8 553.2 941.3 1523.8 Mean Corr = 0.73625 Bbs1 348.2 1125.1 1845.6 Bbs2 165.1 351.6 454.7 Bbs5 634.0 827.7 1339.7 Bbs9 116.8 196.0 291.0 Bbs4 44.7 90.9 213.2 Wdr19 577.1 937.5 1941.0 1110051M20Rik 275.3 424.6 504.9 Tmem237 320.6 421.0 548.3 Ttc26 391.9 693.9 1271.9 Ift74 1178.5 2197.7 4571.0 CEM 1 + Cep290 230.1 687.8 1208.8 Top 10 Genes Fam229b 212.2 312.6 692.5 Dync2li1 1287.1 3096.9 6268.0 Ccdc104 831.8 1388.9 2954.7 Ift80 501.0 1135.0 1722.1

Null module Bbs7 Bbip1 GEO Series "GSE31561" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 36 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31561 Status: Public on Feb 19 2013 Title: Transcriptional analysis of organ-specific toxicity induced by a panPPAR agonist in mice: Identification of organ-specific toxicity biomarkers Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23272042 Summary & Design: Summary: In this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified.

Overall design: Nine wild type mice (strain: C57BL/6J) were randomly divided into three groups - Group-I, II and III. PPM-201 in the vehicle base was administered daily for 14 days at 6 mg/kg body weight dose rate to each mouse in Group-II and at 20mg/kg body weight dose rate to each mouse in Group-III while the mice in Group-I received only the vehicle base. On 15th day, the mice were sacrificed to harvest blood, heart, skeletal muscle, liver and kidney tissues for clinical chemistry, microarray and histopathology analysis. In the clinical chemistry analysis, alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), creatinine kinase (CK, U/L), blood urea nitrogen (BUN, mmol/L), creatinine (umol/L) and lactate dehydrogenase (LDH, U/L) were measured from the blood of each mouse. Two sections of liver, two sections of kidney, one or two sections of skeletal muscle, and one section of heart were prepared from each mouse, stained with hematoxylin and eosin (H&E), and examined by a veterinary pathologist. RNA was extracted and processed as per the established protocol from heart, skeletal muscle, liver and kidney tissue samples of all the 9 mice for profiling with Affymetrix Mouse Genome 430 2.0 Array and in total 36 chips were prepared. Using various quality control measures, the data was analysed for its quality. As it was found to be good in quality, the data from all the 36 chips were used for further analysis. The results from histopathology and clinical chemistry analysis were compared with the gene expression to determine if the dosages selected for the study were associated with findings in target organs.

Background corr dist: KL-Divergence = 0.0965, L1-Distance = 0.0540, L2-Distance = 0.0060, Normal std = 0.4768

0.888 Kernel fit Pairwise Correlations Normal fit

Density 0.444

0.000 CEM 1

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

Pre-normalization Quantiles

Heart vehicleHeart vehiclerep1Heart (0.0101892) vehiclerep2Heart (0.00690426) 6mgkg-1rep3Heart (0.00756589) 6mgkg-1 Heartrep1 (0.00761252) 6mgkg-1 Heartrep2 (0.0122184) 20mgkg-1 Heartrep3 (0.0105766) 20mgkg-1Heart rep1 20mgkg-1(0.0171624)Kidney rep2 (0.0143869) Kidneyvehicle rep3 (0.0117117) Kidneyvehiclerep1 (0.0519009) Kidneyvehiclerep2 (0.0484296) Kidney6mgkg-1rep3 (0.0441469) Kidney6mgkg-1 rep1 (0.0630467) Kidney6mgkg-1 rep2 (0.0691467) Kidney20mgkg-1 rep3 (0.0495299) Kidney20mgkg-1 rep1 Liver 20mgkg-1(0.0274329) rep2 vehicleLiver (0.0328234) rep3 vehiclerep1Liver (0.0494889) (0.0713825) vehiclerep2Liver (0.0326931) 6mgkg-1rep3Liver (0.049854) 6mgkg-1 rep1Liver (0.0324903) 6mgkg-1 rep2Liver (0.0417746) 20mgkg-1 rep3Liver (0.0353002) 20mgkg-1Liver rep1 20mgkg-1(0.0266086)Skeletal rep2 (0.0318742)Skeletal Musclerep3 (0.0278187)Skeletal MusclevehicleSkeletal Musclevehiclerep1 (0.0184089)Skeletal Musclevehiclerep2 (0.00627024)Skeletal Muscle6mgkg-1rep3 (0.014632)Skeletal Muscle6mgkg-1 rep1Skeletal (0.0125041)Muscle6mgkg-1 rep2Skeletal (0.0127381)Muscle20mgkg-1 rep3 (0.0133642)Muscle20mgkg-1 rep1 20mgkg-1(0.017106) rep2 (0.0100919) rep3[ (0.0108147)min ] [ medium ] [ max ] CEM 1 Arl6 194.2 422.6 1910.7 P ( S | Z, I ) = 1.00 Ttc8 122.0 270.5 913.5 Mean Corr = 0.71519 Bbs1 24.5 97.6 415.5 Bbs2 247.6 625.3 1289.3 Bbs5 297.0 546.8 739.2 Bbs9 96.1 246.5 320.1 Bbs4 76.9 188.3 543.3 Wdr19 143.1 205.6 822.4 1110051M20Rik 59.6 563.2 1099.4 Tmem237 124.3 279.8 1035.1 Ttc26 25.4 123.6 453.1 Ift74 152.9 345.7 704.1 CEM 1 + Cep290 74.5 184.4 305.5 Top 10 Genes Fam229b 41.2 365.8 1664.0 Dync2li1 71.6 207.8 1242.7 Ccdc104 357.9 582.0 1433.6 Ift80 255.4 647.3 1617.2

Null module Bbs7 Bbip1 GEO Series "GSE19204" 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=GSE19204 Status: Public on Feb 25 2010 Title: Foxa2 programs Th2-cell mediated innate immunity in the developing lung. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20483781 Summary & Design: Summary: Deletion of the gene encoding Foxa2, a winged helix transcription factor selectively expressed in respiratory epithelial cells, caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia. Loss of Foxa2 induced the recruitment and activation of myeloid dendritic cells (mDCs) and Th2 cells in the lung, and was associated with the increased production of T helper 2 (Th2) cytokines and chemokines. mRNA microarray analysis demonstrated that deletion of Foxa2 induced the expression of a number of mRNAs regulating pulmonary dendritic cell activation, Th2 mediated inflammation, and goblet cell differentiation. The spontaneous pulmonary inflammation and goblet cell metaplasia caused by loss of Foxa2 was inhibited by treatment of newborn Foxa2/ mice with monoclonal IL-4Ralpha antibody. Expression of Foxa2 in non-ciliated secretory cells (Clara cells) in vivo inhibited goblet cell differentiation induced by pulmonary allergen exposure. The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2.

Overall design: To investigate the role of Foxa2 and its downstream targets associated with the Th2 inflammation and goblet cell hyperplasia, RNAs were isolated from the lungs of Foxa2-/- and control littermates at PN15. Lung cRNA was hybridized to the murine genome MOE430 V2 chips.

Background corr dist: KL-Divergence = 0.0292, L1-Distance = 0.0142, L2-Distance = 0.0002, Normal std = 0.6704

0.599 Kernel fit Pairwise Correlations Normal fit

Density 0.300

0.000 CEM 1

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

Pre-normalization Quantiles

control_0412-7control_0525-1 control_0530-1(0.153963) KO_0424-2(0.0525786) KO_0525-2(0.329565) (0.257682)KO_0525-3 (0.0851588) (0.121053) [ min ] [ medium ] [ max ] CEM 1 Arl6 326.2 518.2 565.0 P ( S | Z, I ) = 1.00 Ttc8 152.8 334.7 362.6 Mean Corr = 0.71103 Bbs1 180.3 202.9 248.5 Bbs2 418.3 610.8 915.5 Bbs5 316.2 598.0 830.1 Bbs9 248.7 275.8 349.4 Bbs4 247.4 327.4 405.5 Wdr19 651.6 845.8 939.9 1110051M20Rik 666.7 871.3 1066.9 Tmem237 196.2 245.8 304.6 Ttc26 159.7 203.1 271.6 Ift74 136.0 509.7 606.3 CEM 1 + Cep290 38.8 132.9 159.8 Top 10 Genes Fam229b 159.7 209.4 314.1 Dync2li1 454.6 608.5 667.7 Ccdc104 325.8 678.3 689.0 Ift80 659.0 1169.4 1347.1

Null module Bbs7 Bbip1 GEO Series "GSE31797" 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=GSE31797 Status: Public on Mar 01 2012 Title: Activation of SREBP in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22267724 Summary & Design: Summary: Background: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids.

Results: Activation of SREBP (Sterol Response Element Binding Protein) induced lipogenesis in alveolar epithelial cells, causing neutral lipid accumulation, lung inflammation, and tissue remodeling.

Conclusions: The accumulation of neutral lipids in type II epithelial cells and alveolar macrophages caused lung inflammation, consistent with findings in lipid storage disorders.

Significance: Pulmonary lipotoxicity may contribute to the pathogenesis of lung dysfunction associated with diabetes, obesity, and other metabolic disorders.

Overall design: Genome-wide transcription profiling comparison between doxycycline-exposed SFTPC-rtTAWT/Tg/(tetO)7CMV-CreWT/Tg/Insig1flox/flox/Insig2-/- mice (i.e., Insig1/2/ ) and Insig1flox/flox/Insig2-/- . Three independent pooled RNA from isolated lung type 2 cells of each genotype were used.

Background corr dist: KL-Divergence = 0.0437, L1-Distance = 0.0184, L2-Distance = 0.0004, Normal std = 0.5976

0.674 Kernel fit Pairwise Correlations Normal fit

Density 0.337

0.000 CEM 1

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

Pre-normalization Quantiles

Insig1 flox/floxInsig1 flox/flox Insig1/Insig2 flox/flox Insig1-/-/Insig2 InsigKO_C1 / Insig1-/-/Insig2 InsigKO_C2 /Insig2 / Insig1-/-(0.0771593) InsigKO_C3 -/-/Insig2 InsigKO_E1/ (0.13867) -/-/Insig2 InsigKO_E2 (0.390622) -/-(0.120611) InsigKO_E3 (0.115838)[ min (0.157101) ] [ medium ] [ max ] CEM 1 Arl6 725.0 1109.6 1554.2 P ( S | Z, I ) = 1.00 Ttc8 467.9 573.2 1014.9 Mean Corr = 0.68034 Bbs1 331.6 426.4 637.8 Bbs2 334.5 386.4 528.4 Bbs5 324.3 381.4 695.4 Bbs9 224.2 347.3 439.8 Bbs4 175.7 219.6 277.1 Wdr19 397.0 599.5 804.0 1110051M20Rik 444.0 597.8 717.8 Tmem237 649.8 837.6 948.8 Ttc26 282.4 387.2 597.6 Ift74 849.7 922.1 1796.6 CEM 1 + Cep290 174.3 263.7 474.4 Top 10 Genes Fam229b 146.3 175.2 256.2 Dync2li1 1828.2 2201.7 2660.2 Ccdc104 1294.2 1558.2 2014.8 Ift80 595.3 756.9 871.7

Null module Bbs7 Bbip1 GEO Series "GSE39621" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -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=GSE39621 Status: Public on Dec 27 2012 Title: Expression data from brain, liver and spleen of Npc1-/- mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23094108 Summary & Design: Summary: Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional neurological, lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1-/- mice (Npc1nih)relative to Npc1+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates for the neurological disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gauchers disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1-/- as well as Balb/c Npc1nmf164 mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry.

We used microarrays on the diseased organs, brain, liver and spleen of the Npc1-/- mice to unserstand the molecular changes occur during the progression of NPC diseases. From the data, we have identified 12 potential genes which can be potentially developed as blood-based biomarker. We have also discovered up regulation of innate iimunity genes in all three organs of Npc1-/- mice and functionally validated them in liver and spleen.

Overall design: Brain from 11 female Npc1/ and 16 control female mice (Npc1+/+ and Npc1+/) from 6 age groups (20-25, 37-40, 54-55, 59-62, 67-71 and 81-84 days) were surgically harvested. Liver and spleen from 6 Npc1-/- and 6 Npc1+/- female mice from three age group ( 20-25, 54-55 and 67-71 days) were surgically harvested. Organs were kept in RNA later and stored at -20 ´C until used. RNA was isolated and Affymetrix mouse 430 2.0 array hybridizations were performed by UCLA Clinical Microarray Core, UCLA, Los Angeles, CA, USA. Subsequent raw data were analyzed using DNA-Chip Analyzer (D-Chip) with the .CEL files obtained from AGCC. Data from Npc1-/- mice from all age groups were compared to control mice (Npc1+/- and/or Npc1-/- mice) from all age groups separately for brain, liver and spleen. 'Matrix Table1' corrsponds for brain, 'Matrix Table2' corresponds for liver and 'Matrix Table3' corresponds for spleen. Thresholds for selecting significant genes were set at a relative difference Â³1.5-fold, absolute difference Â³100 signal intensity units and p<0.05. Genes that met all three criteria simultaneously were considered as significant change.

Background corr dist: KL-Divergence = 0.0594, L1-Distance = 0.0598, L2-Distance = 0.0057, Normal std = 0.5712

0.698 Kernel fit Pairwise Correlations Normal fit

Density 0.349

0.000 CEM 1

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

Pre-normalization Quantiles

WT BrainWT 20d Brain Mouse1HET 25d Brain Mouse1 HET(0.0313432) 20d Brain NPCMouse1(0.0140553) 25d Brain NPCMouse1 (0.0162534) 20d Brain HETMouse1 (0.0126289) 25d Brain HETMouse1 (0.00683948) 37d Brain NPCMouse1 (0.0139464) 40d Brain NPCMouse1 (0.016438) 37d Brain HETMouse1 (0.00904119) 40d Brain HETMOuse1 (0.0146449) 54d Brain NPCMouse1 (0.0113522) 55d Brain NPCMouse1 (0.00915357) 54d Brain WTMOuse1 (0.0209893) 55dBrain WTMouse1 (0.0106046) 60d Brain Mouse1HET (0.0180255) 60d Brain Mouse2 HET(0.0120707) 59d Brain NPCMouse1(0.0144495) 62d Brain NPCMouse1 (0.0204085) 59d Brain WTMouse1 (0.0146208) 62dBrain HETMouse1 (0.0124092) 67d Brain Mouse1NPC (0.0187159) 67d Brain HETMouse1(0.019081) 67d Brain HETMouse1 (0.0164592) 81d Brain NPCMouse1 (0.0114723) 82d Brain NPCMouse1 (0.0118277) 82d Brain HETMouse1 (0.0138381) 84d Liver HETMouse1 (0.0162993) 20d Liver Mouse1NPC (0.0146176) 25d Liver Mouse1NPC (0.0298372) 20d Liver Mouse1HET (0.0231359) 25d Liver Mouse1HET (0.0277987) 54 Liver Mouse1NPC (0.0181537) 55d Liver (0.0219696)Mouse1NPC 54d Liver Mouse1HET (0.0196722) 55d Liver Mouse1HET (0.0210364) 67d Liver Mouse1NPC (0.0404608) 67d Liver Mouse2NPC (0.0204903) 67 Liver Mouse1HET (0.0193252) 71d Spleen (0.00947791)Mouse1HET Spleen20dNPC (0.010961) Mouse1 25dSpleenNPC Mouse1 (0.0185343) Spleen20dHET Mouse1 (0.0200526) Spleen25dHET Mouse1 (0.0196972) Spleen54dNPC Mouse1 (0.0230194) 55dSpleenNPC Mouse1 (0.0228344) Spleen54dHET Mouse1 (0.0550539) Spleen55dHET Mouse1 (0.0444037) Spleen67dNPC Mouse1 (0.0222925) 67dSpleenNPC Mouse2 (0.0237655) Spleen67 Mouse1 (0.0214348) 71d (0.0364861)Mouse1 (0.028521)[ min ] [ medium ] [ max ] CEM 1 Arl6 113.9 1278.8 1832.2 P ( S | Z, I ) = 1.00 Ttc8 107.0 586.5 1241.9 Mean Corr = 0.67938 Bbs1 73.5 707.9 1267.1 Bbs2 73.8 441.2 775.7 Bbs5 28.2 400.5 801.9 Bbs9 82.2 155.3 274.0 Bbs4 49.2 186.5 435.7 Wdr19 59.1 509.8 690.3 1110051M20Rik 120.8 1401.5 2001.8 Tmem237 61.0 338.7 548.2 Ttc26 43.5 217.0 405.9 Ift74 74.9 257.1 682.5 CEM 1 + Cep290 30.1 120.5 224.5 Top 10 Genes Fam229b 52.2 409.1 672.1 Dync2li1 24.8 707.0 1043.9 Ccdc104 711.4 1452.9 2774.0 Ift80 135.0 545.9 746.8

Null module Bbs7 Bbip1 GEO Series "GSE13526" 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=GSE13526 Status: Public on Nov 05 2009 Title: Transcript profiling of WT and Nxf2 KO post-natal day 21 testes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19345203 Summary & Design: Summary: In euakryotes, mRNAs must be exported from the nucleus to the cytsoplasm. NXF2 is highly expressed in the mouse male germ cells. We are interested in its function in spermatogenesis, espically in the nuclear RNA export in the testis. To this end, we made Nxf2 mutant mice by gene targeting. In an attempt to identify the mRNA substrates of NXF2, we perform the microarray experiments on testes.

We used microarrays to check the expression profiles of the Nxf2 WT and KO 21d testes on C57BL/6 background.

Overall design: To examine the expression difference between WT and Nxf2 KO testes, we collected testes from juvenile mice of three ages ( 21d, 26d, 28d). Testis weight was similar between WT and KO mice at post-natal day 21. Three pairs of WT and KO 21d testes were chosen for microarray analysis.

Background corr dist: KL-Divergence = 0.0259, L1-Distance = 0.0249, L2-Distance = 0.0010, Normal std = 0.6980

0.619 Kernel fit Pairwise Correlations Normal fit

Density 0.309

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

Nxf2 KO1Nxf2 21d KO2 testisNxf2 21d KO3(0.130984) testisWT1 21d 21d(0.0808744) testisWT2 testis 21d(0.359619) WT3(0.0941203) testis 21d (0.155559) testis (0.178843) [ min ] [ medium ] [ max ] CEM 1 Arl6 1745.8 2092.7 2261.3 P ( S | Z, I ) = 1.00 Ttc8 608.5 758.6 796.8 Mean Corr = 0.68764 Bbs1 915.1 1217.9 1320.3 Bbs2 1306.1 1509.4 1615.7 Bbs5 1458.1 1824.3 1885.0 Bbs9 1021.6 1160.2 1244.4 Bbs4 611.4 674.7 767.8 Wdr19 1386.9 1418.1 1523.6 1110051M20Rik 1751.3 2122.7 2232.3 Tmem237 1189.3 1440.5 1595.3 Ttc26 1396.3 1925.8 1963.9 Ift74 2867.4 3317.3 3479.9 CEM 1 + Cep290 949.2 1221.0 1326.9 Top 10 Genes Fam229b 4998.3 5632.4 5864.4 Dync2li1 1058.2 1334.7 1475.5 Ccdc104 3217.4 3825.8 4195.0 Ift80 2877.7 3351.2 3543.5

Null module Bbs7 Bbip1 GEO Series "GSE23408" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 39 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.925 Kernel fit Pairwise Correlations Normal fit

Density 0.463

0.000 CEM 1

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

Pre-normalization Quantiles

lung_9V/null_lung_9V/null_ 4w_rep1lung_9V/null_ 4w_rep2lung_9V/null_ (0.0121531) 12w_rep1lung_9V/null_ (0.011467) 12w_rep2lung_9V/null_ (0.021172) 18w_rep1lung_9V/null_ (0.0161459) 18w_rep2lung_9V/null_ (0.0352111) 28w_rep1liver_9V/null_ (0.0230226) 28w_rep2liver_9V/null_ (0.0145364) 4w_rep1liver_9V/null_ (0.0131764) 4w_rep2liver_9V/null_ (0.03141) 12w_rep1liver_9V/null_ (0.0237924) 12w_rep2liver_9V/null_ (0.0165389) 18w_rep1liver_9V/null_ (0.0259647) 18w_rep2liver_9V/null_ (0.0335326) 28w_rep1lung_4L_ (0.0199248) 28w_rep2lung_4L_ (0.0150626)4w_rep1lung_4L_ (0.0165438)4w_rep2 (0.0365357)lung_4L_ 12w_rep1 (0.029537)lung_4L_ 12w_rep2 (0.0130358)lung_4L_ 18w_rep1 (0.0245807)lung_4L_ 18w_rep2 (0.0430597)lung_4L_ 28w_rep1 (0.0225039)liver_4L_ 28w_rep2 (0.0507229)liver_4L_ 4w_rep1 (0.0252111)liver_4L_ 4w_rep2 (0.0317918)liver_4L_ 12w_rep1 (0.0206591)liver_4L_ 12w_rep2 (0.020909)liver_4L_ 18w_rep1 (0.0269712)liver_4L_ 18w_rep2 (0.0185474)liver_4L_ 28w_rep1 (0.0222866)lung_WT_ 28w_rep2 (0.0463277)lung_WT_ 28w_rep1 (0.0445334)lung_WT_ 28w_rep2 (0.0422745)lung_WT_ 28w_rep3 (0.026729)liver_WT_ 28w_rep4 (0.0237138)liver_WT_ 28w_rep1 (0.0563654)liver_WT_ 28w_rep2 (0.0149154) 28w_rep3 (0.0106473) (0.0184875)[ min ] [ medium ] [ max ] CEM 1 Arl6 89.9 385.5 1036.5 P ( S | Z, I ) = 1.00 Ttc8 110.0 218.5 507.2 Mean Corr = 0.67826 Bbs1 4.2 86.8 244.4 Bbs2 19.5 228.5 432.1 Bbs5 53.0 191.7 314.3 Bbs9 35.8 185.8 379.0 Bbs4 7.0 87.4 334.8 Wdr19 44.5 204.8 674.6 1110051M20Rik 107.7 482.2 1062.5 Tmem237 130.0 654.9 1343.7 Ttc26 27.3 142.2 349.4 Ift74 76.7 436.3 1099.7 CEM 1 + Cep290 0.4 38.5 267.0 Top 10 Genes Fam229b 40.4 145.5 288.2 Dync2li1 86.9 951.7 2471.7 Ccdc104 202.6 809.0 1575.2 Ift80 8.9 166.2 497.7

Null module Bbs7 Bbip1 GEO Series "GSE9954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 70 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9954 Status: Public on Dec 20 2007 Title: Large-scale analysis of the mouse transcriptome Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18365009 Summary & Design: Summary: We used microarrays to compare gene expression across different murine tissues.

Keywords: Other

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

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

1.449 Kernel fit Pairwise Correlations Normal fit

Density 0.724

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse diaphragm,Mouse diaphragm,Mouse biological diaphragm,Mouse biological spleen,replicateMouse biological spleen,replicateMousebiological 1 (0.0070802) spleen,replicateMousebiological 2 replicate(0.0063466) muscle,Mousebiological 3 replicate(0.00429263) 1 (0.011728)muscle,Mouse biological replicate 2 (0.0079592)muscle,Mouse biological replicate 3 (0.0103445)muscle,Mouse biological replicate 1 liver,(0.00468911)Mouse biological replicate biological2 liver,(0.00451645)Mouse replicate biological3 liver,(0.00426547)Mouse replicate biological4 brain,(0.00531292)Mouse replicate 1 (0.00852563) biological brain,Mouse replicate 2 (0.00899663) biological brain,Mouse replicate 3 (0.00603936) biological lung,Mouse replicate 1 (0.00940855)biological lung,Mouse replicate 2 (0.00540187)biological lung,Mouse replicate 3 (0.00702617)biological kidney,Mouse replicate 1 (0.00314911) kidney,Mousebiological replicate 2 (0.00652499) kidney,Mousebiological 3replicate (0.00297702) adrenalMousebiological replicate 1 (0.00348258)adrenal Mousegland, replicate 2 (0.00446614)biologicaladrenal Mousegland, 3 (0.00382214)biologicalbone Mousegland, replicate marrow, biologicalboneMouse replicate 1 marrow, (0.00322419) biologicalboneMouse replicate 2 marrow, (0.00329236) biologicalboneMouse replicate 3 marrow, (0.00410621) biologicaladiposeMouse replicate 1 (0.0119841) biologicaladiposeMouse tissue, replicate 2 (0.0221962) adiposeMouse biologicaltissue, replicate 3 (0.0085434) pituitaryMouse biologicaltissue, replicate4 (0.010372) pituitaryMouse biologicalgland, replicate 1 (0.00333958)pituitaryMouse biological gland, replicate 2 (0.00442621)pituitaryMouse biological gland, replicate 3 (0.00340599)pituitaryMouse biological gland, replicate 1 (0.0254295)salivaryMouse biological gland, replicate 2 (0.0245175)salivaryMouse biologicalgland, replicate 3 (0.0362602)salivaryMousebiological gland, replicate 4 (0.018558)seminalMousebiological gland, replicate 5 (0.027032)seminalMousebiological vesicle, replicate 1 (0.0148562) seminalMouse vesicle, biological replicate 2 (0.0144449) thymus,Mouse vesicle, biological replicate3 (0.0240153) thymus,Mouse biologicalbiological replicate 1 thymus,Mouse (0.00349504)biological replicatereplicate 2 testis,Mouse (0.00580035)biological replicate 13biological testis,Mouse (0.00541985)(0.00345416) replicate 2 biological testis,Mouse(0.0060088) replicate 3 biological heart,Mouse(0.00602533) replicate 1 (0.0482411)biological heart,Mouse replicate 2 (0.0464509)biological heart,Mouse replicate 3 (0.0768882)biological smallMouse replicate 1 (0.0138619)intestine, smallMouse replicate 2 (0.00854729)intestine, smallMouse biological 3 (0.0104861)intestine, eye,Mouse biological replicate biological eye,Mouse biological replicate biological 1 (0.00986583)eye,Mousereplicate replicate biological 2 (0.0107316)ESMousereplicate 1 cells,(0.0902697) 3 (0.0161645)ESMousereplicate biological2 cells,(0.091969) ESMouse biological3 cells,(0.08356) replicate placenta,Mouse biological replicate 1 placenta,Mouse (0.00474143) biological replicate 2 placenta,Mouse (0.00475605) biological replicate 3 ovary,Mouse (0.00643392) biological replicate biological 1ovary,Mouse (0.00635737) replicate biological 2ovary,Mouse (0.00616229) replicate biological 3fetus,Mouse (0.00747467) replicate 1 (0.00401614)biological fetus,Mouse replicate 2 (0.00494919)biological fetus, replicate 3 (0.00542772)biological replicate 1 (0.00451363) replicate 2 (0.00465641)[ min3 (0.00691248) ] [ medium ] [ max ] CEM 1 Arl6 218.1 558.7 4009.3 P ( S | Z, I ) = 1.00 Ttc8 209.8 418.6 1605.3 Mean Corr = 0.67788 Bbs1 185.1 274.4 842.0 Bbs2 215.6 323.0 925.2 Bbs5 215.0 347.5 2432.2 Bbs9 227.6 306.9 856.8 Bbs4 193.5 245.0 350.1 Wdr19 188.9 278.5 871.4 1110051M20Rik 273.5 563.1 1683.7 Tmem237 209.0 573.7 1902.0 Ttc26 170.0 284.2 657.8 Ift74 233.0 518.8 1668.2 CEM 1 + Cep290 138.9 237.9 572.7 Top 10 Genes Fam229b 170.1 303.4 16732.5 Dync2li1 250.3 526.0 1775.9 Ccdc104 315.4 924.5 10584.3 Ift80 233.3 454.1 1170.2

Null module Bbs7 Bbip1 GEO Series "GSE19534" 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=GSE19534 Status: Public on Jul 22 2010 Title: Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic vocalization Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20056137 Summary & Design: Summary: Alpha-synuclein is an abundant protein implicated in synaptic function and plasticity, but the molecular mechanism of its action is not understood. Missense mutations and gene duplication/triplication events result in Parkinson's disease, a neurodegenerative disorder of old age with impaired movement and emotion control. Here, we systematically investigated the striatal as well as the cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome-wide microarray survey in order to gain hypothesis-free molecular insights into the physiological function of alpha-synuclein. A genotype-dependent, specific and strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed in all brain regions from postnatal age until old age and could be validated by qPCR. In view of the co-localization and heterodimer formation of FOXP1 with FOXP2, a transcription factor with a well established role for vocalization, and the reported regulation of both alpha-synuclein and FOXP2 expression during avian song learning, we performed a detailed assessment of mouse movements and vocalizations in the postnatal period. While there was no difference in isolation-induced behavioral activity in these animals, the alpha-synuclein-deficient mice exhibited an increased production of isolation-induced ultrasonic vocalizations (USVs). This phenotype might also reflect the reduced expression of the anxiety-related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we identified an early behavioral consequence of alpha-synuclein deficiency and accompanying molecular changes, which supports the notion that the neural connectivity of sound or emotion control systems is affected.

Overall design: Factorial design comparing SNCA knock-out mice with wild type littermates in two different tissues (striatum, cerebellum) at two different timepoints (6 and 21 month)

Background corr dist: KL-Divergence = 0.0459, L1-Distance = 0.0209, L2-Distance = 0.0004, Normal std = 0.5868

0.680 Kernel fit Pairwise Correlations Normal fit

Density 0.340

0.000 CEM 1

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

Pre-normalization Quantiles

cerebellumcerebellum wildcerebellum type wild 6cerebellum month type wild 6 cerebellum replicatemonth type SNCA 6 cerebellum replicatemonth 1 knockout (0.0252437)SNCA striatumreplicate 2 knockout (0.00772551)SNCA 6 striatummonth wild 3 knockout(0.0199096) 6type replicatestriatummonth wild 6 month 6type replicatestriatummonth wild1 (0.0249749)6 replicatemonth type replicatestriatum SNCA2 (0.0430641)6 replicatemonth 1 striatum knockout (0.0183998)SNCA3 (0.0469824) replicate 2 cerebellum knockout (0.0109801)SNCA 6 month 3 cerebellum knockout(0.0422204) 6 wildreplicatemonthcerebellum type 6 wildreplicatemonth 121 cerebellum(0.0483657) typemonth wildreplicate 221 cerebellum(0.036004) replicatetypemonth wild 321 cerebellum(0.0512669) replicatetypemonth 1 SNCA (0.0653116) 21cerebellum replicatemonth 2knockout SNCA (0.0501765)cerebellum replicate 3knockout SNCA (0.0270991) 21striatum month 4knockout SNCA (0.0569191) 21striatum replicatemonthwild knockout 21typestriatum replicatemonthwild 1 21 (0.077647) 21 typemonthstriatum replicatemonthwild 2 21 (0.0789425) replicatetypemonthstriatum replicateSNCA 3 21 (0.0544463) replicatemonth striatum1knockout SNCA (0.0220851)4 (0.0286054) replicate 2knockout SNCA (0.0476629) 21 month 3knockout (0.0267232) 21 replicatemonth 21 replicatemonth 1[ (0.0228691)min replicate 2 (0.0434619) ] 3 (0.022913)[ medium ] [ max ] CEM 1 Arl6 1073.8 1738.0 1999.5 P ( S | Z, I ) = 1.00 Ttc8 617.3 936.0 1154.4 Mean Corr = 0.67772 Bbs1 379.0 590.6 796.0 Bbs2 367.1 609.0 916.3 Bbs5 323.2 571.8 747.0 Bbs9 153.7 239.2 329.3 Bbs4 79.4 117.7 163.2 Wdr19 251.8 315.2 379.0 1110051M20Rik 1228.3 1516.6 1774.5 Tmem237 552.4 683.2 934.4 Ttc26 80.1 121.0 170.7 Ift74 403.8 571.9 698.0 CEM 1 + Cep290 89.0 232.6 329.1 Top 10 Genes Fam229b 224.5 370.6 597.1 Dync2li1 457.2 675.4 980.7 Ccdc104 1328.3 2248.5 2872.6 Ift80 523.5 740.3 930.1

Null module Bbs7 Bbip1 GEO Series "GSE26745" 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=GSE26745 Status: Public on Jul 21 2011 Title: Comparison of total and polyribosome-associated mRNA levels in male Fmr1 KO mice and male WT littermates Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21784246 Summary & Design: Summary: The Fragile X Mental Retardation Protein, FMRP, is thought to regulate the translation of a specific set of neuronal mRNAs on polyribosomes. Therefore, we prepared polyribosomes on sucrose gradients and purified mRNA specifically from these fractions, as well as the total mRNA levels, to determine whether a set of mRNAs might be changed in its % association with polyribosomes in the absence of FMRP in the KO mouse model.

No significant differences were found, other than the Fmr1 transcript itself, in total mRNA levels or % polyribosome association that withstood multiple test correction, in P7 Fmr1 KO mouse cerebral cortex compared with WT littermates..

Overall design: We prepared polyribosomes on sucrose gradients from 6 littermate pairs of Fmr1 KO and WT littermates (FVB background, P7 males, cerebral cortex) and purified RNA from both polyribosomal fractions and input to the gradient, reflecting total mRNA levels for comparison.

Background corr dist: KL-Divergence = 0.1111, L1-Distance = 0.0459, L2-Distance = 0.0033, Normal std = 0.4392

0.968 Kernel fit Pairwise Correlations Normal fit

Density 0.484

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 P7 mouseWT P7 cerebralmouseWT P7 cerebralmouseWT cortex, P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseWT cortex,polyribosomal P7 cerebralmouseFmr1 cortex,polyribosomalRNA, KO biologicalcerebralFmr1 cortex,polyribosomalRNA, P7 mouseKO biologicalFmr1 cortex,polyribosomalRNA, P7replicate cerebral mouseKO biologicalFmr1 polyribosomalRNA, P7replicate 1 cerebral mouseKO(0.0419093) cortex,biologicalFmr1 RNA, P7replicate 2 cerebral mouseKO(0.0209646) cortex,polyribosomalbiologicalFmr1 RNA, P7replicate 3 cerebral mouseKO(0.0541859) cortex,polyribosomalbiologicalWT P7replicate P74 cerebralmouse (0.0631424) cortex,polyribosomalRNA,mouseWT replicate P75 biologicalcerebral (0.0475581) cortex,polyribosomalRNA,cerebralmouseWT P76 biological (0.0615242) cortex,polyribosomalRNA,cerebralmouse WT replicatecortex, P7 biological polyribosomalRNA,cerebralmouse WT replicatecortex,total 1 P7(0.0924081) biological cortical RNA,cerebralmouse WT replicatecortex,total 2 P7(0.0529338) biological cortical lysateRNA,cerebralmouse Fmr1 replicatecortex,total 3 (0.0277065) biological RNA,KOcortical lysatecerebral Fmr1 replicatecortex,total P74 biological(0.0412887) mouseRNA,KOcortical lysate Fmr1 replicatecortex,total P75 biological(0.0556094) cerebralmouseRNA,KOcortical lysatereplicateFmr1 total P76 biological(0.0248644) cerebralmouseRNA,KO cortical cortex,lysatereplicateFmr1 1 P7 (0.0538189) biological cerebralmouseRNA,KO cortex,totallysatereplicateFmr1 2 P7 (0.0415931) biologicalcortical cerebralmouseRNA,KO cortex,totalreplicate 3 P7 (0.0303337) biologicalcortical lysatecerebralmouse cortex,totalreplicate 4 (0.0327983) RNA,cortical lysatecerebral cortex,totalreplicate 5 biological (0.0301029) RNA,cortical lysate cortex,total[ 6 biological min(0.0421744) RNA,cortical lysatereplicate total biological RNA,cortical ]lysatereplicate 1 (0.0349767) biological RNA, lysatereplicate 2 (0.0304025) biological[ RNA, replicatemedium 3 (0.0231498) biological replicate 4 (0.0242851) replicate 5 (0.0357385)] 6 (0.0365306)[ max ] CEM 1 Arl6 3538.7 4086.3 6284.1 P ( S | Z, I ) = 1.00 Ttc8 855.9 1296.2 2104.1 Mean Corr = 0.66351 Bbs1 154.9 201.7 311.5 Bbs2 48.8 69.4 90.0 Bbs5 338.7 440.6 591.9 Bbs9 87.2 126.4 200.9 Bbs4 30.8 42.1 64.9 Wdr19 58.1 74.6 96.4 1110051M20Rik 1282.5 1832.6 2765.1 Tmem237 456.5 571.7 780.0 Ttc26 90.4 105.4 154.1 Ift74 293.2 899.9 1253.9 CEM 1 + Cep290 165.5 291.6 538.6 Top 10 Genes Fam229b 116.2 353.8 502.8 Dync2li1 702.1 1231.7 1717.2 Ccdc104 3046.1 4521.7 6018.5 Ift80 54.2 73.3 88.4

Null module Bbs7 Bbip1 GEO Series "GSE39458" 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=GSE39458 Status: Public on Dec 31 2012 Title: Differential gene expression of Kit+Sca1+Lin- (KSL) cells from arthritic versus control mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The involvement of mature hematopoietic cells in disease pathogenesis is well recognized. However it is not clear how if and how primitive progenitors might contribute to inflammatory disease processes.

This microarray experiment is used together with data from functional assays to determine how primitive progenitors are altered in a mouse model of autoimmune arthritis and how this in turn might contribute to the disease process.

Overall design: All the mice used in this study were C57BL/6 background strain. G7 mice are congenic with C57BL/6 but with MHC II I-Ab replaced with MHC II I-Ag7.

Background corr dist: KL-Divergence = 0.0145, L1-Distance = 0.0305, L2-Distance = 0.0010, Normal std = 0.8466

0.495 Kernel fit Pairwise Correlations Normal fit

Density 0.247

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

KSL cells_B6xG7_sortedKSL cells_KRN_sortedKSL cells_KRNxG7_sortedLin+_B6xG7_sorted (0.221536)Lin+_KRN_sorted (0.0982427)Lin+_KRNxG7_sorted (0.190466)(0.177391) (0.169035) (0.143329)[ min ] [ medium ] [ max ] CEM 1 Arl6 59.4 279.3 345.0 P ( S | Z, I ) = 1.00 Ttc8 22.6 218.3 356.9 Mean Corr = 0.65622 Bbs1 28.5 138.1 196.8 Bbs2 37.2 81.5 121.0 Bbs5 11.0 71.4 98.0 Bbs9 87.8 139.4 148.5 Bbs4 41.6 73.0 110.1 Wdr19 33.0 88.2 99.5 1110051M20Rik 84.7 329.0 333.6 Tmem237 122.8 743.6 846.4 Ttc26 23.3 79.1 103.2 Ift74 51.6 273.9 416.7 CEM 1 + Cep290 94.5 319.6 386.3 Top 10 Genes Fam229b 50.9 66.4 76.4 Dync2li1 83.7 166.2 218.7 Ccdc104 455.5 533.6 844.7 Ift80 471.5 561.9 601.9

Null module Bbs7 Bbip1 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, (0.0211743)0mg/kg/day rep1 lungPFOS, (0.035851)0mg/kg/day rep2 liverPFOS, (0.0277601)0mg/kg/day rep2 lungPFOS, (0.0312154)0mg/kg/day rep3 liverPFOS, (0.0358214)0mg/kg/day rep3 lungPFOS, (0.0643158)0mg/kg/day rep4 liverPFOS, (0.0654032)5mg/kg/day rep4 lungPFOS, (0.0347241)5mg/kg/day rep5 liverPFOS, (0.024928)5mg/kg/day rep5 lungPFOS, (0.0195423)5mg/kg/day rep1 liverPFOS, (0.0265091)5mg/kg/day rep1 lungPFOS, (0.0441855)5mg/kg/day rep2 liverPFOS, (0.0405196)5mg/kg/day rep2 lungPFOS, (0.0194631)5mg/kg/day rep3 liverPFOS, (0.0210397)5mg/kg/day rep3 lungPFOS, (0.0183086)5mg/kg/day rep4 liverPFOS, (0.0433184)10mg/kg/day rep4 lungPFOS, (0.0200199)10mg/kg/day rep5 liver PFOS, (0.0308723)10mg/kg/day rep5 lungPFOS, (0.0223065)10mg/kg/day rep1 liverPFOS, 10mg/kg/day(0.0189172) rep1 lungPFOS, 10mg/kg/day(0.0185353) rep2 liverPFOS, 10mg/kg/day(0.0311503) rep2 lungPFOS, 10mg/kg/day(0.0396024) rep3 liverPFOS, 10mg/kg/day(0.00757806) rep3 lungPFOS, 10mg/kg/day(0.0406431) rep4 liverPFOS, (0.0229228) rep4 lungPFOS, (0.0829728) rep5 liver (0.0590764) rep5 [(0.0313234) min ] [ medium ] [ max ] CEM 1 Arl6 114.2 402.8 557.9 P ( S | Z, I ) = 1.00 Ttc8 204.5 477.2 671.0 Mean Corr = 0.65106 Bbs1 52.1 145.7 204.5 Bbs2 100.7 309.6 462.7 Bbs5 120.1 193.9 294.6 Bbs9 85.8 154.4 219.3 Bbs4 44.3 53.7 74.2 Wdr19 86.3 254.8 366.2 1110051M20Rik 197.8 408.6 557.3 Tmem237 266.7 481.0 809.7 Ttc26 60.1 165.7 270.0 Ift74 132.1 580.6 764.6 CEM 1 + Cep290 64.3 109.2 207.3 Top 10 Genes Fam229b 65.2 177.9 251.0 Dync2li1 315.1 879.3 1238.5 Ccdc104 556.2 937.9 1257.1 Ift80 346.0 548.1 678.2

Null module Bbs7 Bbip1 GEO Series "GSE14007" 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=GSE14007 Status: Public on Dec 23 2008 Title: Gene expression of growth plate of mouse. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The growth plate is histomorphologically classified into four zones {resting zone (RZ), proliferating zone (PZ), maturing zone (MZ) and hypertrophic zone (HZ)}. Gene expression profile analyses of 4 zones were performed using microarrays.

Overall design: We performed global analysis of gene expression in tibias from nine-day-old mice. Chondrocytes layer was microdissected en-block from four anatomically distinct growth plate zones, and RNA expression was analyzed using microarrays.Chondrocytes from four anatomical zones were isolated from tibias of two mice. The eight samples were named after the mouse (1 or 2) and the growth plate zone, such as resting zone of 1st mouse (RZ01), 2nd mouse (RZ02), proliferation zone (PZ01, PZ02), maturing zone (MZ01, MZ02) and hypertrophic zone (HZ01, HZ02).

Background corr dist: KL-Divergence = 0.0621, L1-Distance = 0.0278, L2-Distance = 0.0013, Normal std = 0.5305

0.752 Kernel fit Pairwise Correlations Normal fit

Density 0.376

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_RZ_01MOUSE_RZ_02MOUSE_PZ_01 (0.246974)MOUSE_PZ_02 (0.301038)MOUSE_MZ_01 (0.0392518)MOUSE_MZ_02 (0.0842933)MOUSE_HZ_01 (0.0603059)MOUSE_HZ_02 (0.0663651) (0.0990296) (0.102742) [ min ] [ medium ] [ max ] CEM 1 Arl6 511.9 730.8 997.0 P ( S | Z, I ) = 1.00 Ttc8 176.8 332.8 793.4 Mean Corr = 0.66234 Bbs1 176.5 253.9 364.8 Bbs2 172.6 425.6 808.9 Bbs5 121.9 172.7 309.2 Bbs9 134.1 196.2 390.4 Bbs4 16.1 104.8 237.9 Wdr19 219.0 285.0 468.7 1110051M20Rik 476.6 597.2 717.0 Tmem237 532.1 1206.1 1813.9 Ttc26 129.1 277.5 445.7 Ift74 204.1 449.5 859.1 CEM 1 + Cep290 73.2 126.0 169.6 Top 10 Genes Fam229b 176.1 396.2 438.6 Dync2li1 177.1 296.1 662.9 Ccdc104 1205.1 2244.1 3337.1 Ift80 240.4 536.5 838.0

Null module Bbs7 Bbip1 GEO Series "GSE20696" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE20696 Status: Public on Sep 30 2010 Title: Expression profiling of 3T3-L1 adipogenesis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20887899 Summary & Design: Summary: 3T3-L1 pre-adipocyte cells were grown to confluence and induced to differentiate in adipogeneic media.

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

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

0.651 Kernel fit Pairwise Correlations Normal fit

Density 0.325

0.000 CEM 1

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

Pre-normalization Quantiles

3T3-L1_t1_rep13T3-L1_t1_rep23T3-L1_t2_rep1 (0.12117)3T3-L1_t2_rep2 (0.10891)3T3-L1_t3_rep1 (0.219396)3T3-L1_t3_rep2 (0.141432)3T3-L1_t4_rep1 (0.108453)3T3-L1_t4_rep2 (0.123188) (0.0799723) (0.0974787) [ min ] [ medium ] [ max ] CEM 1 Arl6 931.1 1337.7 1695.2 P ( S | Z, I ) = 1.00 Ttc8 612.7 1308.0 1508.9 Mean Corr = 0.64628 Bbs1 101.9 139.9 269.4 Bbs2 212.1 363.0 478.5 Bbs5 359.8 414.7 479.0 Bbs9 98.7 189.2 234.0 Bbs4 59.4 72.1 84.2 Wdr19 108.2 291.0 488.1 1110051M20Rik 319.0 772.7 935.0 Tmem237 483.7 848.7 970.5 Ttc26 91.8 388.2 591.4 Ift74 440.8 1030.4 1236.8 CEM 1 + Cep290 129.5 185.4 228.6 Top 10 Genes Fam229b 221.1 410.2 551.0 Dync2li1 502.1 1006.8 1718.3 Ccdc104 2311.2 2470.1 2782.6 Ift80 353.4 1193.5 1382.2

Null module Bbs7 Bbip1 GEO Series "GSE40856" 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=GSE40856 Status: Public on Apr 01 2013 Title: Non-tumor/tumor intestinal tissue of control or intestine-specific HAI-1 deficient Apc(Min/+) mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23447577 Summary & Design: Summary: To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods.

Mouse small intestine tumor tissue or background mucosa lacking macroscopically visible tumors were proceeded to RNA extraction and hybridization on microarrays (Affymetrix Mouse Genome 430 2.0 Array).

Overall design: Non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox) mice and non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox)/Vil-Cre mice were analysed. The experiment was repeated respectively.

Background corr dist: KL-Divergence = 0.0508, L1-Distance = 0.0245, L2-Distance = 0.0009, Normal std = 0.5637

0.708 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

Nontumor_Control1Nontumor_Control2Tumor_Control1 (0.179925)Tumor_Control2 (0.181453)Nontumor_KO1 (0.0409393)Nontumor_KO2 (0.0492199)Tumor_KO1 (0.112389)Tumor_KO2 (0.0935855) (0.106262) (0.236227) [ min ] [ medium ] [ max ] CEM 1 Arl6 36.3 287.0 358.7 P ( S | Z, I ) = 1.00 Ttc8 32.2 141.4 218.3 Mean Corr = 0.64256 Bbs1 5.7 26.6 65.8 Bbs2 68.7 142.2 394.6 Bbs5 49.5 142.3 202.6 Bbs9 61.3 89.8 106.1 Bbs4 2.9 21.5 42.2 Wdr19 13.5 121.4 419.6 1110051M20Rik 146.2 240.5 367.6 Tmem237 116.4 473.6 686.9 Ttc26 25.7 101.0 129.9 Ift74 145.8 387.9 415.7 CEM 1 + Cep290 69.1 117.4 144.0 Top 10 Genes Fam229b 3.8 69.6 82.7 Dync2li1 30.8 190.4 305.0 Ccdc104 171.9 586.1 820.3 Ift80 53.1 92.7 140.4

Null module Bbs7 Bbip1 GEO Series "GSE29685" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 132 -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=GSE29685

Background corr dist: KL-Divergence = 0.3964, L1-Distance = 0.0812, L2-Distance = 0.0207, Normal std = 0.2500 GEO Series "GSE26096" 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=GSE26096 Status: Public on Jan 03 2011 Title: Widespread targeted chromatin remodeling during the initial phase of somatic cell reprogramming [expression] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21211784 Summary & Design: Summary: Despite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency or developmentally related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.

Overall design: Gene expression was measured by Affymetric microarrays during the initial phase of the reprogramming of mouse embryonic fibroblasts.

Background corr dist: KL-Divergence = 0.0618, L1-Distance = 0.0293, L2-Distance = 0.0012, Normal std = 0.5376

0.765 Kernel fit Pairwise Correlations Normal fit

Density 0.383

0.000 CEM 1

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

Pre-normalization Quantiles

Serum-starvedSerum-starved 96control, hr doxycycline 96control, biological hr doxycyclineMEFdox0Div_rep1 biological induction, rep1MEFdox0Div_rep2 (0.208817) induction, rep2 biologicalMEFdox1Div_rep1 (0.0824462) (0.0922882) biologicalMEFdox1Div_rep2 rep1 (0.104911) (0.0596356)MEFdox2Div_rep1 rep2 (0.0764749) (0.158028)MEFdox2Div_rep2 (0.0724171) (0.0776837) (0.0672994)[ min ] [ medium ] [ max ] CEM 1 Arl6 671.4 812.4 1100.9 P ( S | Z, I ) = 1.00 Ttc8 351.0 682.5 964.9 Mean Corr = 0.62468 Bbs1 43.4 81.2 142.7 Bbs2 166.7 228.4 312.2 Bbs5 194.7 333.3 495.9 Bbs9 114.1 165.8 248.6 Bbs4 47.1 52.8 59.0 Wdr19 122.7 256.1 311.3 1110051M20Rik 703.5 792.5 958.9 Tmem237 1286.8 1437.9 1858.9 Ttc26 109.6 150.6 176.5 Ift74 1054.3 1495.8 2045.4 CEM 1 + Cep290 94.6 143.6 155.5 Top 10 Genes Fam229b 239.9 343.0 535.3 Dync2li1 696.1 908.9 1682.8 Ccdc104 2259.8 2506.9 2651.1 Ift80 354.9 703.9 1146.3

Null module Bbs7 Bbip1 GEO Series "GSE11201" 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=GSE11201 Status: Public on Apr 18 2008 Title: Coordinated Regulation of Signaling Pathways and Biological Processes during Liver Development Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: Understanding congenital liver disease requires elucidation of the signaling pathways and transcriptional events in the developing liver. Comprehensive assessment of gene expression between 10.5 and 16.5 dpc in the developing mouse liver and comparison with adult liver and non-hepatic embryonic tissue was validated with real-time PCR and in situ hybridization. The broad nature of the analysis provides insights into patterns of genetic control of hepatogenesis. Pathways implicated in human disease are highly regulated at the transcriptional level. Rather than activating or inhibiting a pathway or biological process by altering the expression of a single signaling molecule, transcriptional changes in large numbers of genes in a pathway or process are regulated in a coordinated manner. For example, both TGF-beta and Notch signaling is inhibited during hepatogenesis not just by decreasing transcription of multiple pathway members, but also with a complementary increase in the transcription of a pathway inhibitor. Similarly, genes related to specific biological processes exhibit strong temporal synchronization in which multiple members of the pathway have similar transcriptional regulation over time. Global coordination of signaling or functional families at the transcriptional level may be a mechanism to produce robustness of the desired outcomes. In addition, this comprehensive analysis provides a database for the further study of transcriptional events during liver development by identifying liver-specific, highly regulated genes.

Keywords: time course

Overall design: In order to provide transcriptional profile of the developing liver compared both to normal adult liver and non-hepatic embryonic tissueswe performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for embryonic liver samples at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc), embryo-minus liver tissues at 10.5, 11.5, 12.5, and 14.5 dpc, and normal 10-week-old adult mouse liver. Each sample consisted of at least five embryos.

Background corr dist: KL-Divergence = 0.0374, L1-Distance = 0.0354, L2-Distance = 0.0018, Normal std = 0.6265

0.637 Kernel fit Pairwise Correlations Normal fit

Density 0.318

0.000 CEM 1

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

Pre-normalization Quantiles

baselinebaseline liver sampledevelopmental liver sampleatdevelopmental T0, biological at developmentalliver T0, samplebiological developmentalliver rep1 sample at(0.0356405) developmental liver T105,rep2 sample at(0.102152) biological developmental liverT105, sampleat biological developmental liverT115, rep1 sampleat biological(0.0678693) developmental liverT115, rep2 sampleat biological(0.0250751) developmental liverT125, rep1 sampleat biological(0.0446502) developmental liverT125, rep2 sampleat biological(0.0254726) developmental liverT135, rep1 sampleat biological(0.0317144) developmental liverT135, rep2 sampleat biological(0.0196123) embryonic liverT145, rep1 sampleat biological(0.0415581) embryonic liverT145, rep2 liver sampleat biological(0.0166657)embryonic T165,sample rep1 liver at biological(0.0320717)embryonic T165, sampleat rep2 liver105, biological(0.022057) samplebiologicalat rep1 liver115, (0.0410248) samplebiologicalat rep2 125,rep1 (0.0564047) biologicalat(0.16104) 145,rep1[ biological (0.103881)min rep1 (0.116755) rep1] (0.0563552)[ medium ] [ max ] CEM 1 Arl6 106.2 251.2 1408.5 P ( S | Z, I ) = 1.00 Ttc8 129.7 227.6 598.0 Mean Corr = 0.64524 Bbs1 53.2 116.9 304.7 Bbs2 13.6 146.5 369.9 Bbs5 43.6 138.3 242.8 Bbs9 115.4 166.5 207.8 Bbs4 55.2 127.7 216.4 Wdr19 327.6 424.1 884.6 1110051M20Rik 247.9 418.3 1202.1 Tmem237 164.3 469.7 787.7 Ttc26 49.8 141.8 545.0 Ift74 134.0 285.0 2420.7 CEM 1 + Cep290 34.8 121.2 208.5 Top 10 Genes Fam229b 100.1 156.5 309.7 Dync2li1 791.0 945.4 1226.6 Ccdc104 489.0 697.3 2098.4 Ift80 281.4 396.4 474.2

Null module Bbs7 Bbip1 GEO Series "GSE17096" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17096 Status: Public on Dec 09 2011 Title: mRNA composition of IRP1 mRNPs in mouse tissues Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21940823 Summary & Design: Summary: Affymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP1 (iron regulatory protein 1).

Overall design: All the microarray procedures were conducted at the EMBL Genomics Core Facility using standard Affymetrix protocols. In brief, approximately 120ng of immunoprecipitated RNA was used as input to a two-step amplification procedure to generate biotin-labeled RNA fragments for hybridization to the Affymetrix GeneChip Mouse Genome 430 2.0 array (Eukaryotic Sample and Array Processing manual 701024 Rev.3). Intensity values for the hybridizations were obtained either using RMA, calculations done in bioconductor (www.bioconductor.org) or MAS5, calculated using Affymetrix GCOS package. MAS5 calculated intensities were further quantile normalized using bioconductor.

Background corr dist: KL-Divergence = 0.0791, L1-Distance = 0.0942, L2-Distance = 0.0182, Normal std = 0.5457

0.753 Kernel fit Pairwise Correlations Normal fit

Density 0.377

0.000 CEM 1

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

Pre-normalization Quantiles

IRP1 immunoprecipitationIRP1 controlIRP1 immunoprecipitationimmunoprecipitationIRP1 duodenum controlIRP1 immunoprecipitationimmunoprecipitationIRP1 replica duodenumduodenum controlIRP1 1 (0.0283387) immunoprecipitationimmunoprecipitationIRP1 replicareplica liverduodenum controlIRP1 21 replica (0.0346038)(0.0494411) immunoprecipitationimmunoprecipitationIRP1 replica 1 (0.0902328) liverliver controlIRP1 2 replicareplica (0.0268506) immunoprecipitationimmunoprecipitationIRP1 21 (0.0388716) (0.0205646) spleenliver controlIRP1 replica replica immunoprecipitationimmunoprecipitationIRP1 2 (0.015981) 1spleenspleen control(0.018251)IRP1 replicareplica immunoprecipitationimmunoprecipitationIRP1 2bone1spleen control (0.0136687)(0.020401)IRP1 marrow replica immunoprecipitationimmunoprecipitationIRP1 replica bone2bone control (0.0185624)IRP1 marrow marrow1 (0.0308731) immunoprecipitationimmunoprecipitationIRP1 replicareplica brainbone control replicamarrow 21 (0.0212864) (0.0192037)immunoprecipitation 1 replica (0.167658)brainbrain replica replica2 (0.0265105)[ 21min (0.0920568)(0.117175)brain replica ] 2 (0.149469)[ medium ] [ max ] CEM 1 Arl6 84.1 143.7 878.5 P ( S | Z, I ) = 1.00 Ttc8 48.9 115.0 956.3 Mean Corr = 0.61488 Bbs1 57.8 100.8 1023.2 Bbs2 82.1 131.4 270.7 Bbs5 56.6 81.1 354.0 Bbs9 59.5 92.1 157.5 Bbs4 30.5 47.1 95.7 Wdr19 94.9 194.1 713.1 1110051M20Rik 167.8 222.7 1431.5 Tmem237 120.6 203.9 1105.6 Ttc26 31.2 50.9 108.2 Ift74 53.8 79.6 251.3 CEM 1 + Cep290 51.8 113.9 271.9 Top 10 Genes Fam229b 67.2 97.2 251.0 Dync2li1 79.9 128.3 328.4 Ccdc104 106.9 294.1 1072.7 Ift80 136.8 779.8 953.1

Null module Bbs7 Bbip1 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(0.0351299)Day Positive 17 Batch (0.0133062)GFPDay Positive 71Batch GFP(0.0188771)Day Negative 1 8Batch (0.0285538)GFPDay Positive 18 Batch (0.0615549)GFPDay Negative 51Batch GFP(0.0200475)Day Negative 15 Batch (0.0255165)GFPDay Positive 61 Batch GFP(0.0616711)Day Negative 62Batch GFP(0.260427)Day Positive 27 Batch (0.0991018)GFPDay Negative 72Batch GFP(0.040335)Day Positive 28 Batch (0.0508759)GFPDay Negative 82Batch GFP(0.0341053)Mouse Positive2 Batch(0.0516525) embryonicMouse 2Batch (0.055433) embryonic stem2 (0.0249905) cell stem derived cell derived cardiomyocytes[ min cardiomyocytes ] 1 (0.0471289) 2 (0.0712934)[ medium ] [ max ] CEM 1 Arl6 433.3 663.0 1527.5 P ( S | Z, I ) = 1.00 Ttc8 233.1 375.7 612.7 Mean Corr = 0.61670 Bbs1 62.4 119.3 163.0 Bbs2 77.8 165.8 274.3 Bbs5 212.8 300.3 547.3 Bbs9 108.3 155.9 243.5 Bbs4 11.1 53.7 108.0 Wdr19 119.8 241.1 290.4 1110051M20Rik 404.1 521.0 731.4 Tmem237 701.4 921.9 1292.4 Ttc26 190.5 279.0 700.5 Ift74 466.2 680.5 1675.7 CEM 1 + Cep290 58.0 111.0 231.4 Top 10 Genes Fam229b 21.5 63.0 174.0 Dync2li1 289.4 446.2 1102.3 Ccdc104 487.2 695.3 1545.2 Ift80 229.4 330.6 547.0

Null module Bbs7 Bbip1 GEO Series "GSE51365" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 28 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51365 Status: Public on Oct 18 2013 Title: Latent gammaherpesvirus 68 infection induces distinct transcriptional changes in different organs Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24155394 Summary & Design: Summary: Previous studies identified a role for latent herpesvirus infection in cross-protection to infection and exacerbation of chronic inflammatory diseases. Here, we compared the gene expression signature from livers, spleens and brains of mice infected with wild-type gammaherpesvirus 68 (MHV68), a mutant virus defective in the establishment of latency (ORF73.stop) or mockulum. We identified over 600 genes differentially expressed in organs of mice latently infected with MHV68 and found distinct sets of genes linked to different pathways were altered in spleen compared to liver. Several of the most differentially expressed latency-specific genes (e.g. IFNÎ³, Cxcl9, Ccl5) are associated with known latency-specific phenotypes.

Overall design: RNA was extracted from livers, spleens and brains of 7-9 week old male C57Bl/6 mice infected with gammaherpesvirus 68 (MHV68), a virus defective in establishment of latency (ORF73.stop) or mockulum. RNA from 3-4 mice per treatment was pooled and analyzed by M430 2.0 Affymetrix Gene Chip. Three biologic replicates were analyzed for all conditions, except mock livers, for which four biologic replicates were analyzed.

Background corr dist: KL-Divergence = 0.0674, L1-Distance = 0.0734, L2-Distance = 0.0082, Normal std = 0.6075

0.657 Kernel fit Pairwise Correlations Normal fit

Density 0.328

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

Null module Bbs7 Bbip1 GEO Series "GSE15610" 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=GSE15610 Status: Public on Dec 22 2009 Title: Knockout of the selenocysteine tRNA (Trsp) gene in mouse macrophage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19863805 Summary & Design: Summary: Comparative analysis of gene expression in bone marrow-derived macrophages (BMDM) from trsp knockout mice (Trspfl/fl-LysM-Cre+/-) and Control (Trspfl/fl-LysM-Cre-/-) mice.

Selenium, a micronutrient whose deficiency in the diet causes immune dysfunction and inflammatory disorders, exerts its physiological effects partly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins, is mediated by Sec tRNA[Ser]Sec. To identify macrophage-specific selenoprotein function, we generated mice with the Sec tRNA[Ser]Sec gene specifically deleted in myeloid cells. These mutant mice were devoid of the selenoproteome in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix. Therefore, selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages.

Overall design: We have generated mice in which we have selectively removed the selenocysteine tRNA gene (trsp) in macrophages under the control of LysM-Cre promoter. Microarray analysis was performed on RNA samples taken from bone marrow-derived macrophages in knockout and control mice. 1. Control unstimulated 2. Knockout unstimulated 3. Control lipopolysaccharide (LPS) stimulated (4h) 4. Knockout LPS stimulated (4h). Three replicates for each condition. Thus, a total of 12 samples.

Background corr dist: KL-Divergence = 0.0769, L1-Distance = 0.0376, L2-Distance = 0.0023, Normal std = 0.4963

0.823 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

Control_untreated_replicateControl_untreated_replicateControl_untreated_replicateKnockout_untreated_replicate 1Knockout_untreated_replicate (0.0957386) 2Knockout_untreated_replicate (0.0305202) 3Control_4h (0.100339)Control_4h 1 (0.0549063) lipopolysaccharide_replicateControl_4h 2 (0.0415833) lipopolysaccharide_replicateKnockout_4h 3 (0.174923) lipopolysaccharide_replicateKnockout_4h lipopolysaccharide_replicateKnockout_4h 1 (0.123264) lipopolysaccharide_replicate 2 (0.136165) lipopolysaccharide_replicate 3 (0.0712179) 1 [(0.0537209) min 2 (0.0717544) ] 3 (0.0458685)[ medium ] [ max ] CEM 1 Arl6 77.4 324.2 444.4 P ( S | Z, I ) = 1.00 Ttc8 31.8 194.2 318.5 Mean Corr = 0.60801 Bbs1 4.2 31.6 62.3 Bbs2 5.5 31.1 69.0 Bbs5 6.7 135.1 226.4 Bbs9 38.0 109.0 176.5 Bbs4 3.2 59.0 176.4 Wdr19 45.2 77.2 141.2 1110051M20Rik 155.9 215.4 261.0 Tmem237 343.5 754.2 1196.0 Ttc26 22.2 49.7 84.7 Ift74 61.9 235.5 450.3 CEM 1 + Cep290 38.1 102.0 175.6 Top 10 Genes Fam229b 6.0 64.5 121.2 Dync2li1 61.7 107.9 150.4 Ccdc104 159.4 469.4 720.1 Ift80 28.3 116.5 216.0

Null module Bbs7 Bbip1 GEO Series "GSE16585" 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=GSE16585 Status: Public on Oct 19 2009 Title: Expression profiling of P14 and P28 mouse retina from 4 genotypes: +/+, Rorb-/- , +/+;CrxpNrl and Rorb-/-;CrxpNrl Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19805139 Summary & Design: Summary: Rorb is essential for rod photoreceptor development in the mouse retina. Using Affymetrix mouse GeneChips, we have generated expression profiles of the +/+, Rorb-/- , +/+;CrxpNrl and Rorb-/-;CrxpNrl retina at P14 and P28.

In this dataset, we include the expression data obtained from retina of wt and mutants. These data are used to obtain 1189 genes that are differentially expressed in Rorb-/- vs wt.

Overall design: 31 total samples were analyzed

Background corr dist: KL-Divergence = 0.1975, L1-Distance = 0.0336, L2-Distance = 0.0018, Normal std = 0.3390

1.177 Kernel fit Pairwise Correlations Normal fit

Density 0.588

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

P14 +/+ P14retina, +/+ biologicalP14retina, +/+ biologicalP14retina, rep1 +/+ biologicalP14retina,(0.0271691) rep2 Rorb-/- biologicalP14(0.0176847) rep3 Rorb-/-retina, P14(0.0255392) rep4 biologicalRorb-/- retina, P14(0.0289933) Rorb-/- biologicalretina, rep1P14 +/+;CrxpNrl (0.0100877)biologicalretina, rep2P14 +/+;CrxpNrl biological(0.0196438) rep3P14 retina, +/+;CrxpNrl (0.0214873) rep4P14 biologicalretina, +/+;CrxpNrl (0.0176454)P14 biologicalretina, rep1Rorb-/-;CrxpNrlP14 biologicalretina,(0.0220832) rep2Rorb-/-;CrxpNrlP14 biological(0.0228963) rep3Rorb-/-;CrxpNrl retina,P14 (0.0385207) rep4 Rorb-/-;CrxpNrl biologicalretina,P28 (0.0461623) +/+ biologicalretina, P28rep1retina, +/+ biologicalretina,(0.0056174) biologicalP28rep2retina, +/+ biological(0.0173602) biologicalP28rep3retina, rep1 +/+ (0.0267521) biologicalP28rep4retina,(0.0210063) rep2 Rorb-/- (0.0325736) biologicalP28(0.0107664) rep3 Rorb-/-retina, P28(0.0337501) rep4 biologicalRorb-/- retina, P28(0.0229338) Rorb-/- biologicalretina, rep1P28 +/+;CrxpNrl (0.0422181)biologicalretina, rep2P28 +/+;CrxpNrl biological(0.0342982) rep3P28 retina, +/+;CrxpNrl (0.0207795) rep4P28 biologicalretina, Rorb-/-;CrxpNrl (0.0121057)P28 biologicalretina, rep1Rorb-/-;CrxpNrlP28 biological(0.0174039) rep2Rorb-/-;CrxpNrl retina,P28 (0.0137101) rep3 Rorb-/-;CrxpNrl biologicalretina, (0.0326831) biologicalretina, rep1 biologicalretina,(0.0220418) rep2 biological(0.0374547) [rep3 min (0.153457) rep4 ] (0.145175) [ medium ] [ max ] CEM 1 Arl6 2431.0 8511.7 10146.9 P ( S | Z, I ) = 1.00 Ttc8 2174.7 4616.7 6169.4 Mean Corr = 0.59764 Bbs1 691.0 1462.6 1885.2 Bbs2 878.3 1452.8 2139.5 Bbs5 597.2 2224.4 4497.0 Bbs9 304.8 905.4 1465.2 Bbs4 91.0 157.4 217.4 Wdr19 391.8 545.5 656.3 1110051M20Rik 1353.3 1772.1 2702.1 Tmem237 1411.6 3364.5 4557.8 Ttc26 162.8 299.3 376.4 Ift74 702.5 1056.5 1397.8 CEM 1 + Cep290 619.2 1473.3 1945.6 Top 10 Genes Fam229b 441.8 689.2 1206.6 Dync2li1 644.6 893.3 1229.2 Ccdc104 1748.9 2792.1 3432.4 Ift80 1033.4 1272.0 1443.2

Null module Bbs7 Bbip1 GEO Series "GSE27546" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 51 -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=GSE27546 Status: Public on Feb 28 2011 Title: Effects of HMGN variants on cellular transcription profile Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21278158 Summary & Design: Summary: HMGN (high mobility group N) is a family of intrinsically disordered nuclear proteins that binds to nucleosomes, alters the structure of chromatin and affects transcription. A major unresolved question is the extent of functional specificity, or redundancy, between the various members of the HMGN protein family.

Here we analyze the transcriptional profile of cells in which the expression of various HMGN proteins has been either deleted or doubled. The results reveal an HMGN-variant specific effect on the fidelity of the cellular transcription profile, indicating that functionally, the various HMGN subtypes are not fully redundant.

Overall design: RNA was collected from either primary knock-out MEFs or SV40-transformed MEFs and MIN6 cells over expressing various HMGN proteins and mutants and hybridized to Affymetrix arrays. We obtained a double ammount of HMGN proteins in MEFs and MIN6 cells by retroviral infection and subsequent selection procedure. We collected all infected cells (pools, not clones) in order to eliminate the effect of viral integration in the genome.

Background corr dist: KL-Divergence = 0.0270, L1-Distance = 0.0406, L2-Distance = 0.0025, Normal std = 0.6975

0.572 Kernel fit Pairwise Correlations Normal fit

Density 0.286

0.000 CEM 1

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

Pre-normalization Quantiles

MEFs HMGN1MEFs HMGN1 knockMEFs outHMGN1 knockMEFs rep outHMGN1 1knockMEFs (0.0227598) rep outHMGN1 2WTMEFs (0.0185647) rep rep HMGN1 3WT MEFs 1(0.0174352) (0.0168166) rep HMGN3 WT MEFs2 (0.0173978) rep HMGN3 knock MEFs3 (0.0146754) outHMGN3 knockMEFs rep outHMGN3 1knockMEFs (0.0210871) rep outHMGN3 2WTMEFs (0.0186163) rep rep HMGN3 3WT MEFs 1(0.0190014) (0.0210863) rep HMGN5 WT MEFs2 (0.0217927) rep HMGN5 knock MEFs3 (0.0185696) outHMGN5 knockMEFs rep outHMGN5 1knockMEFs (0.0178085) rep outHMGN5 2WTMEFs (0.0139719) rep rep HMGN5 3WT MEFs 1(0.0141798) (0.0172557) rep empty WT MEFs2 (0.0156991) rep vector empty MEFs3 (0.0150957) OEvector emptyMEFs rep OE1vector HMGN1 (0.00231428)MEFs rep OE2 HMGN1 (0.00333005)OEMEFs rep rep 3 HMGN1 (0.00323779)OE1MEFs (0.00250199) rep HMGN2 OE2MEFs (0.00130486) rep HMGN2 OE3MEFs (0.00654939) rep HMGN2 OE1MEFs (0.00641314) rep HMGN3a OE2MEFs (0.0066883) rep HMGN3a 3MEFs OE (0.0062011) rep HMGN3aMEFs OE1 (0.00194886) rep HMGN5MEFs OE2 (0.00494129) rep HMGN5 OEMEFs 3 (0.00189854) rep HMGN5 OE1MEFs (0.00533556) rep HMGN5SE OE2MEFs (0.00795793) rep HMGN5SE 3MEFs (0.00532731) OE repHMGN5SEMEFs OE1 (0.00482005) repHMGN1_N2swapMEFs OE2 (0.00353475) repHMGN1_N2swapMEFs 3 (0.00310591) HMGN1_N2swapMEFs rep 1 HMGN1_N3swap (0.00389571)MEFs rep 2 HMGN1_N3swap (0.00769177)MEFs rep 3 HMGN1_N3swap (0.00577879)MIN6 rep 1empty (0.0119579)MIN6 rep vector 2empty (0.00842828)MIN6 rep OEvector 3empty (0.00961048)MIN6 rep OE1vector HMGN1 (0.0615072)MIN6 rep OE2 HMGN1 (0.0385227)OEMIN6 rep rep 3 HMGN1 (0.0405518)OE1MIN6 (0.0577761) rep HMGN3a OE2MIN6 (0.0472037) rep HMGN3a 3 MIN6OE (0.0654271) rep HMGN3a OE1 (0.0799236) rep OE2 (0.0748209) rep 3 (0.0876792)[ min ] [ medium ] [ max ] CEM 1 Arl6 601.9 1268.5 2608.4 P ( S | Z, I ) = 1.00 Ttc8 460.9 962.7 2223.7 Mean Corr = 0.59342 Bbs1 34.7 140.6 572.2 Bbs2 38.3 182.1 848.5 Bbs5 199.5 359.5 472.9 Bbs9 60.0 142.2 314.3 Bbs4 21.3 65.6 92.6 Wdr19 131.7 180.7 261.3 1110051M20Rik 436.3 643.4 1027.1 Tmem237 626.9 811.7 2078.9 Ttc26 100.9 257.9 608.1 Ift74 668.8 1283.7 2357.4 CEM 1 + Cep290 59.8 170.4 625.9 Top 10 Genes Fam229b 61.6 155.2 372.1 Dync2li1 309.6 523.1 1645.6 Ccdc104 1133.1 2128.8 3130.8 Ift80 208.0 726.6 2021.4

Null module Bbs7 Bbip1 GEO Series "GSE37546" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE37546 Status: Public on Apr 26 2012 Title: Disturbed Hepatic Carbohydrate Management During High Metabolic Demand in Medium-Chain Acyl-CoA Dehydrogenase (MCAD)-deficient Mice Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18459129 Summary & Design: Summary: Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD-/- mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD-/- mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1a (Pgc-1a) and decreased peroxisome proliferator-activated receptor alpha (Ppar a) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD-/- mice in both conditions,suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD-/- mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD-/- mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD-/- mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD-/- mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD-/- mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation.

Overall design: Total RNA obtained from Liver ( 20 samples) , where comparing 4 groups, consisting out of 5 biological replicates, all groups where fasted for 12 hrs, and half of them where injected with LPS ( 100ug/20gr BW) or vehicle

Background corr dist: KL-Divergence = 0.1254, L1-Distance = 0.0278, L2-Distance = 0.0011, Normal std = 0.4081

0.979 Kernel fit Pairwise Correlations Normal fit

Density 0.489

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 (0.0257129)Control 2 (0.0598499)Control 3 (0.0576184)Control 4 (0.019712)Control 5 (0.0347228)Control + LPS 1Control + (0.0560474) LPS 2Control + (0.0506701) LPS 3Control + (0.0207059) LPS 4MCAD + (0.0425656) LPS 15MCAD (0.0552564)(0.0296138) 2MCAD (0.0444805) 3MCAD (0.0349009) 4MCAD (0.0269817) 5MCAD (0.0234922) +MCAD LPS 1 + MCAD(0.115014) LPS 2 + MCAD(0.0702804) LPS 3 + MCAD(0.106427) LPS 4 + (0.0771763) LPS 5 (0.0487718) [ min ] [ medium ] [ max ] CEM 1 Arl6 100.4 219.7 860.5 P ( S | Z, I ) = 1.00 Ttc8 49.3 108.7 222.3 Mean Corr = 0.59159 Bbs1 24.6 41.7 82.1 Bbs2 40.4 59.6 82.6 Bbs5 57.4 145.8 290.6 Bbs9 57.2 125.5 217.1 Bbs4 31.1 39.7 61.6 Wdr19 28.6 35.3 44.4 1110051M20Rik 30.1 40.4 52.1 Tmem237 73.3 249.8 417.1 Ttc26 30.4 43.4 82.7 Ift74 138.9 412.1 784.1 CEM 1 + Cep290 32.7 64.6 108.3 Top 10 Genes Fam229b 20.4 27.8 36.4 Dync2li1 48.0 70.1 200.7 Ccdc104 624.4 1206.6 1885.0 Ift80 75.6 131.8 201.4

Null module Bbs7 Bbip1 GEO Series "GSE32095" 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=GSE32095 Status: Public on Feb 22 2012 Title: GPR120 mediates high-fat diet induced obesity Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22343897 Summary & Design: Summary: Analysis of GPR120 which play roles for the fatty acid sensor in adipose tissue. Results provide insight into the transcriptional effects caused by the loss of the GPR120 proteins and provide further insight into their functions.

Overall design: GPR120 KO mice and the corresponding wild-type with normal diet(ND) or high fat diet(HFD), were subjected to Affymetrix Mus musculus microarrays. Epididymal adipose tissue and liver were analyzed in triplicates.

Background corr dist: KL-Divergence = 0.1001, L1-Distance = 0.0645, L2-Distance = 0.0080, Normal std = 0.4859

0.914 Kernel fit Pairwise Correlations Normal fit

Density 0.457

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

EpididymalLiver adipose GPR120KOEpididymal GPR120KOLiver HFD adipose GPR120KO Epididymal#427 HFD (0.0261124)GPR120KO #427Liver HFD adipose (0.00800216)GPR120KO Epididymal#428 HFD (0.051515)GPR120KO #428Liver HFD adipose (0.0145899)WT Epididymal#429 HFDHFD (0.0431845)WT #546#429Liver HFD adipose (0.0413539) (0.0120001)WT #546Epididymal HFD (0.0237492) WT #547Liver HFD adipose(0.038773) WT #547Liver HFD (0.0285618) WT #560Epididymal HFDND (0.043222) #686 #560Liver (0.0314131) adipose(0.0264799) WTEpididymal ND WT#687Liver ND (0.0371534) adipose #687WTEpididymal ND (0.04453) WT#690Liver ND (0.0585723) adipose #690GPR120KOEpididymal (0.0434625) GPR120KOLiver ND adipose GPR120KO#718Epididymal ND (0.0274068) GPR120KO#718Liver ND (0.0374393)adipose GPR120KO#719Epididymal ND (0.0276416) GPR120KO#719 ND (0.0581434)adipose #720 ND (0.0360016) WT#720 ND (0.0513831) #686[ min(0.189309) ] [ medium ] [ max ] CEM 1 Arl6 103.7 609.4 1378.9 P ( S | Z, I ) = 1.00 Ttc8 83.3 327.1 650.3 Mean Corr = 0.58501 Bbs1 5.0 115.4 258.3 Bbs2 16.4 159.5 637.0 Bbs5 153.6 299.3 1897.3 Bbs9 47.0 146.8 341.9 Bbs4 10.6 59.6 90.2 Wdr19 38.5 150.5 313.9 1110051M20Rik 43.2 197.7 594.8 Tmem237 146.4 526.7 958.0 Ttc26 42.6 102.7 339.9 Ift74 137.7 243.9 2263.4 CEM 1 + Cep290 16.1 89.9 473.9 Top 10 Genes Fam229b 5.5 284.8 9059.5 Dync2li1 59.4 298.9 680.6 Ccdc104 614.2 1329.6 5227.6 Ift80 56.8 147.7 532.8

Null module Bbs7 Bbip1 GEO Series "GSE34423" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 40 -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=GSE34423 Status: Public on Dec 14 2011 Title: Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice [Expression array]. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21455306 Summary & Design: Summary: Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.

Overall design: 2932 days old male B6C3F1/Crl (C57BL/6 x C3H/He ) mice were obtained from Charles River Laboratories (Germany). Animals were allowed to acclimatise for 5 days prior to being randomly divided into two treatment groups (n = 10) and phenobarbital (Sigma 04710, 0.05% (w/v) in drinking water) was administered to one group through ad libitum access to drinking water for 28 days. Mice were checked daily for activity and behavior and sacrificed on the last day of dosing (day 28). Blood was withdrawn for PK analysis and target (liver) and non-target (kidney) tissues removed, split into several sections, frozen in liquid nitrogen and stored at 80´C for subsequent analyses. Total RNA from liver and kidney was purified and processed for Affymetrix gene expression profiling while genomic DNA was prepared for promoter array based methylome analysis using the Methylated DNA immunoprecipitation (MeDIP) procedure. Remaining tissue material was used for chromatin immunoprecipitation (ChIP) to analyze histone modifications at individual promoters. Plasma samples were also collected to evaluate phenobarbital exposure in individual animals by LC-MS.

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0729, L2-Distance = 0.0087, Normal std = 0.5583

0.829 Kernel fit Pairwise Correlations Normal fit

Density 0.415

0.000 CEM 1

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

Pre-normalization Quantiles

PB_Kidney_Control_5PB_Kidney_Control_1PB_Kidney_Control_9 PB_Kidney_Control_4(0.0227524) PB_Kidney_Control_10(0.0161912) PB_Kidney_Control_8(0.0201801) PB_Kidney_Control_3(0.0341421)PB_Kidney_Control_7 (0.02399) PB_Kidney_Control_2(0.0198892) PB_Kidney_Control_6(0.0196371) PB_Liver_Control_10(0.0228377) PB_Liver_Control_9(0.0156071) PB_Liver_Control_2(0.0218737) (0.0146654)PB_Liver_Control_3 (0.0178422)PB_Liver_Control_6 (0.0525581)PB_Liver_Control_5 (0.0141543)PB_Liver_Control_4 (0.0180593)PB_Liver_Control_8 (0.028727)PB_Liver_Control_1 (0.0515932)PB_Liver_Control_7 (0.0225001)PB_Kidney_treated_20 (0.0290265)PB_Kidney_treated_18 (0.0260367)PB_Kidney_treated_12PB_Kidney_treated_11 (0.0262279)PB_Kidney_treated_17 (0.0271027)PB_Kidney_treated_16 (0.016708)PB_Kidney_treated_14 (0.024962)PB_Kidney_treated_15 (0.0254374)PB_Kidney_treated_13 (0.0206874)PB_Kidney_treated_19 (0.0275385)PB_Liver_treated_12 (0.0388756)PB_Liver_treated_13 (0.0252707)PB_Liver_treated_14 (0.0181046) (0.0184637)PB_Liver_treated_15 (0.0260926)PB_Liver_treated_11 (0.0244343)PB_Liver_treated_16 (0.0370003)PB_Liver_treated_18 (0.0238271)PB_Liver_treated_19 (0.0183523)PB_Liver_treated_20 (0.0166852)PB_Liver_treated_17 (0.0281456) (0.0286925) (0.0351284)[ min ] [ medium ] [ max ] CEM 1 Arl6 172.1 1166.1 1519.4 P ( S | Z, I ) = 1.00 Ttc8 126.1 637.2 957.7 Mean Corr = 0.58274 Bbs1 6.4 251.6 408.0 Bbs2 9.4 231.1 407.5 Bbs5 44.6 190.9 304.0 Bbs9 19.8 148.1 256.7 Bbs4 20.5 91.5 163.1 Wdr19 114.8 195.3 284.4 1110051M20Rik 106.7 321.3 485.1 Tmem237 205.9 2127.5 4288.2 Ttc26 22.1 277.9 374.6 Ift74 135.9 425.3 572.5 CEM 1 + Cep290 15.1 125.6 320.9 Top 10 Genes Fam229b 5.0 155.1 246.8 Dync2li1 106.3 785.2 1058.3 Ccdc104 467.6 1341.5 1703.0 Ift80 110.7 325.3 514.1

Null module Bbs7 Bbip1 GEO Series "GSE11870" 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=GSE11870 Status: Public on Jul 23 2008 Title: Gene expression changes in primary aortic endothelial cells during expression of dominant negative PPAR gamma (V290M). Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18676352 Summary & Design: Summary: Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).

Overall design: We generated transgenic mice specifically targeting expression of dominant negative human PPAR gamma to the endothelium using an endothelial-specific promoter (vascular endothelial cadherin or CDH5). Primary aortic endothelial cells were isolated from 10 non-transgenic and 10 EC-DN mice by Dominion Pharmakine (http://www.pharmakine.com/). For each group, 5 cultures of cells were established. Each culture was derived from 2 mice and remained separate from the other cultures. Cellular RNA was prepared using conventional methods and quality was assessed using the Bioanalyzer 2100 (Agilent Technologies). For the microarray hybridizations, RNA from 3 of the cultures in each group was used. All the microarray procedures were conducted at the University of Iowa DNA Core facility using standard Affymetrix protocols. In brief, approximately 50 ng of total RNA was used as input to a two-step amplification procedure (NuGen, http://www.nugeninc.com/) to generate biotin-labeled RNA fragments for hybridization to the Affymetrix GeneChip Mouse Genome 430 2.0 array.

Background corr dist: KL-Divergence = 0.0338, L1-Distance = 0.0226, L2-Distance = 0.0006, Normal std = 0.6536

0.621 Kernel fit Pairwise Correlations Normal fit

Density 0.310

0.000 CEM 1

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

Pre-normalization Quantiles

PrimaryPrimary aortic endothelialPrimary aortic endothelialPrimary aortic cells, endothelialPrimary aortic Non_transgenic_control_1 cells, endothelialPrimary aortic Non_transgenic_control_2 cells, endothelial aortic Non_transgenic_control_3 cells, endothelial transgenic_PPARG_V290M_1 cells, (0.0948303) transgenic_PPARG_V290M_2 cells, (0.157372)[ transgenic_PPARG_V290M_3min (0.0907029) ] (0.114718) (0.420448)[ medium (0.121928) ] [ max ] CEM 1 Arl6 564.2 879.0 921.4 P ( S | Z, I ) = 1.00 Ttc8 234.3 553.8 653.9 Mean Corr = 0.61062 Bbs1 82.5 239.9 278.7 Bbs2 200.6 493.6 585.2 Bbs5 544.2 676.0 954.4 Bbs9 117.0 391.2 468.1 Bbs4 162.4 424.9 455.1 Wdr19 448.2 562.1 727.3 1110051M20Rik 1119.6 1446.7 1731.6 Tmem237 1353.3 1476.7 2162.5 Ttc26 203.8 291.2 330.0 Ift74 482.9 550.5 758.3 CEM 1 + Cep290 87.1 178.8 194.5 Top 10 Genes Fam229b 577.3 857.2 970.1 Dync2li1 751.3 1426.5 1466.5 Ccdc104 792.8 1044.4 1196.7 Ift80 878.0 1039.6 1583.0

Null module Bbs7 Bbip1 GEO Series "GSE4481" 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=GSE4481 Status: Public on Dec 15 2006 Title: C-type natriuretic peptide regulates endochondral ossification through p38 MAP kinase-dependent pathways_2 Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: C-type natriuretic peptide (CNP) has been recently identified as an important anabolic regulator of endochondral bone growth, but the molecular mechanism mediating these effects are not completely understood. Here we demonstrate that CNP activates the p38 MAP kinase pathway in chondrocytes and that pharmacological inhibition of p38 blocks the anabolic effects of CNP in a tibia organ culture system. We further show that CNP stimulates endochondral bone growth largely through expansion of the hypertrophic zone of the growth plate, while delaying mineralization. Both effects are reversed by p38 inhibition. We performed Affymetrix microarray analyses to identify CNP target genes in the organ culture system. These studies confirmed that hypertrophic chondrocytes are the main targets of CNP signaling in the growth plate, potentially because cGMP-dependent kinases I and II, important transducers of CNP signaling and are expressed at much higher levels in these cells than in other areas of the tibia. One of the genes most strongly induced by CNP was the Ptgs2 gene, encoding Cox2. Real-time PCR confirmed that Cox2 expression was induced by CNP in hypertrophic chondrocytes, but surprisingly in a p38-independent manner. Moreover, Cox2 inhibition in contrast to p38 inhibition - did not block the anabolic effects of CNP. In summary, our data identify novel target genes of CNP and demonstrate that the p38 pathway is a novel, essential mediator of CNP effects on endochondral ossification, with potential implications for numerous skeletal diseases.

Keywords: Growth plate zone comparison and treatment response analysis

Overall design: Tibiae from E15.5 day old embryonic mice were isolated and cultured in minimal media in the presence of vehicle, BSA/HCl (1mM), or C-type natriuretic peptide, CNP (10-6M). On the sixth day of treatment cultured tibias were micro-dissected into the resting/proliferating, hypertrophic, and mineralized areas. Distinct zones from approximately 24 bones were pooled together, from which RNA was isolated using the Qiagen RNeasy Lipid Extraction Kit. Once the quality of total RNA from three independent trials was determined using the Agilent 2100 bioanalyzer, microarray analyses were performed at the London Regional Genomics Centre using MOE430_2.0 Affymetrix arrays. Results were analyzed using GeneSpring 7.2 software.

Background corr dist: KL-Divergence = 0.1409, L1-Distance = 0.0266, L2-Distance = 0.0011, Normal std = 0.3892

1.025 Kernel fit Pairwise Correlations Normal fit

Density 0.513

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

3BSA R/P3BSA (0.0697058) H3BSA (0.00924634) M3CNP (0.0402936) R/P3CNP (0.0657135) H3CNP (0.0764708) M2BSA (0.0417262) R/P2BSA (0.113029) H2BSA (0.0102777) M2CNP (0.038768) R/P2CNP (0.119691) H2CNP (0.0382007) M4BSA (0.0707962) R/P4BSA (0.0758971) H4BSA (0.0217875) M4CNP (0.0408057) R/P4CNP (0.065504) H4CNP (0.0293703) M (0.0727159) [ min ] [ medium ] [ max ] CEM 1 Arl6 830.7 1177.1 2496.5 P ( S | Z, I ) = 1.00 Ttc8 454.4 621.2 1387.2 Mean Corr = 0.57051 Bbs1 286.9 490.8 630.9 Bbs2 103.4 205.4 397.5 Bbs5 147.5 333.5 743.9 Bbs9 219.6 326.7 416.8 Bbs4 52.8 105.9 155.9 Wdr19 339.1 479.2 672.6 1110051M20Rik 431.8 590.5 670.5 Tmem237 835.6 1076.9 2283.9 Ttc26 169.5 356.1 540.4 Ift74 378.1 658.6 2032.7 CEM 1 + Cep290 109.0 266.7 747.7 Top 10 Genes Fam229b 47.6 248.8 599.9 Dync2li1 563.9 909.7 1436.8 Ccdc104 1151.7 2552.0 4651.9 Ift80 340.3 686.9 1115.7

Null module Bbs7 Bbip1 GEO Series "GSE24207" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 73 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24207 Status: Public on Nov 18 2010 Title: mRNA analysis in different mouse tissues Organism: Mus musculus Experiment type: Third-party reanalysis Platform: GPL1261 Pubmed ID: 21088282 Summary & Design: Summary: The functioning of a specific tissue depends on the expression pattern of the different genes. We used microarrays to compare gene expression across different murine tissues, to get a better understanding in the expression pattern and functioning of the different tissues. With this analysis, we were not only able to identify genes that were specifically expressed in a spicific tissue but, as important, we also identified genes that were specifically repressed in a tissue, compared to al the other analysed tissues.

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

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

1.542 Kernel fit Pairwise Correlations Normal fit

Density 0.771

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse diaphragm,Mouse diaphragm,Mouse biological diaphragm,Mouse biological spleen,replicateMouse biological spleen,replicateMousebiological 1 (0.00886504) spleen,replicateMousebiological 2 replicate(0.00806786) muscle,Mousebiological 3 replicate(0.00595973) 1 (0.00673832)muscle,Mouse biological replicate 2 (0.00872472)muscle,Mouse biological replicate 3 (0.00670967)muscle,Mouse biological replicate 1 liver,(0.00547457)Mouse biological replicate biological2 liver,(0.00499545)Mouse replicate biological3 liver,(0.00611992)Mouse replicate biological4 brain,(0.00473428)Mouse replicate 1 (0.00944793) biological brain,Mouse replicate 2 (0.00781633) biological brain,Mouse replicate 3 (0.014851) biological lung,Mouse replicate 1 (0.00825296)biological lung,Mouse replicate 2 (0.0044965)biological lung,Mouse replicate 3 (0.00697793)biological kidney,Mouse replicate 1 (0.00194616) kidney,Mousebiological replicate 2 (0.00174904) kidney,Mousebiological 3replicate (0.00176237) adrenalMousebiological replicate 1 (0.00234917)adrenal Mousegland, replicate 2 (0.0014178)biologicaladrenal Mousegland, 3 (0.00238422)biologicalbone Mousegland, replicate marrow, biologicalboneMouse replicate 1 marrow, (0.00268803) biologicalboneMouse replicate 2 marrow, (0.00266568) biologicalboneMouse replicate 3 marrow, (0.00319368) biologicaladiposeMouse replicate 1 (0.00690812) biologicaladiposeMouse tissue, replicate 2 (0.00497425) adiposeMouse biologicaltissue, replicate 3 (0.00661753) pituitaryMouse biologicaltissue, replicate4 (0.00527559) pituitaryMouse biologicalgland, replicate 1 (0.0255662)pituitaryMouse biological gland, replicate 2 (0.00295678)pituitaryMouse biological gland, replicate 3 (0.00582725)pituitaryMouse biological gland, replicate 1 (0.021891)salivaryMouse biological gland, replicate 2 (0.0182423)salivaryMouse biologicalgland, replicate 3 (0.0328086)salivaryMousebiological gland, replicate 4 (0.0128703)seminalMousebiological gland, replicate 5 (0.0125058)seminalMousebiological vesicle, replicate 1 (0.0140767) seminalMouse vesicle, biological replicate 2 (0.00713648) thymus,Mouse vesicle, biological replicate3 (0.00639539) thymus,Mouse biologicalbiological replicate 1 thymus,Mouse (0.00156521)biological replicatereplicate 2 testis,Mouse (0.0118108)biological replicate 13biological testis,Mouse (0.00499085)(0.00706139) replicate 2 biological testis,Mouse(0.00411058) replicate 3 biological heart,Mouse(0.00306646) replicate 1 (0.0379387)biological heart,Mouse replicate 2 (0.0313137)biological heart,Mouse replicate 3 (0.0827784)biological smallMouse replicate 1 (0.00511405)intestine, smallMouse replicate 2 (0.00518514)intestine, smallMouse biological 3 (0.00433761)intestine, eye,Mouse biological replicate biological eye,Mouse biological replicate biological 1 (0.00702233)eye,Mousereplicate replicate biological 2 (0.00651474)placenta,Mousereplicate 1 (0.0738509) 3 (0.00563215)placenta,Mousereplicate 2biological (0.0844079) placenta,Mouse 3biological (0.0649105) replicate ovary,Mouse biological replicate biological 1ovary,Mouse (0.00444852) replicate biological 2ovary,Mouse (0.00529855) replicate biological 3pancreaticMouse (0.00503857) replicate 1 (0.00268421) pancreaticMouse replicate acini,2 (0.00178323) pancreaticMouse biological acini,3 (0.00264784) pancreaticMouse biological acini, replicate pancreaticMouse biological islets, replicate 1pancreaticCell-line, (0.0293226) biological islets, replicate 2Cell-line, (0.0374711) MIN6, biological islets, replicate 3Cell-line, biological(0.0340813) MIN6, biological replicate 1 biological (0.0213575)MIN6, replicate replicate 2 biological (0.0181317) replicate 1 (0.0132578)3 (0.0225106) replicate 2 (0.0168848)[ min 3 (0.0210293) ] [ medium ] [ max ] CEM 1 Arl6 110.5 641.7 5438.5 P ( S | Z, I ) = 1.00 Ttc8 73.6 415.1 2412.4 Mean Corr = 0.56519 Bbs1 3.4 140.7 1340.3 Bbs2 13.4 190.6 899.9 Bbs5 10.0 304.3 4724.6 Bbs9 50.3 247.5 1097.5 Bbs4 13.4 130.5 371.4 Wdr19 36.8 201.2 832.6 1110051M20Rik 144.0 511.7 2309.8 Tmem237 26.8 562.8 3417.9 Ttc26 33.5 236.1 765.3 Ift74 26.8 598.8 2984.7 CEM 1 + Cep290 3.4 180.8 801.8 Top 10 Genes Fam229b 6.7 214.0 25122.1 Dync2li1 90.5 541.7 2434.4 Ccdc104 267.8 1361.1 19192.9 Ift80 20.1 404.4 1819.8

Null module Bbs7 Bbip1