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: 45 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. Rps6kl1 Dnajc21 Num ofGenesinQueryGeneset:45.CEMs:1. Overview ofCo-ExpressionModules(CEMs)withDatasetWeighting Hspa14 Mrps27 Mrps30 Mrps23 Mrps34 Mrps10 Mettl17 Gcn1l1 Rps27l Mrpl21 Mrpl17 Mrpl38 Mrpl33 Mrpl19 Mrpl24 Mrpl14 Mrpl54 Mrpl50 Mrpl45 Mrpl44 Mrpl16 Mrpl46 Rps17 Rps10 Rps25 Rps11 Rps18 Rps13 Rpl7l1 Apex1 Mrps5 Prmt3 Srp68 Serp1 Abcf1 Rpl27 Mrpl4 Mrpl2 Rpl3l Rps9 Canx Rps7 Qtrt1

Mrpl2 Mrps10 Mrpl46 Mrps34 Mrpl16 Mrps23 Mrpl44 Mrps30 Apex1 Mrps27 Mrpl45 Rpl7l1 Mrpl4 Mrpl50 Mrpl54 Rps27l Qtrt1 Mrpl14 Rpl27 Mrpl24 Prmt3 Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 0.0 Singletons CEM 1(339datasets) Scale ofaveragePearsoncorrelations 0.2 0.4 0.6 0.8 1.0 Gadd45gip1 Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page1 Mrps18b Timm23 Timm13 Exosc4 Mrps35 Mrps17 Mrps28 Mrps27 Mrps30 Mrps23 Mrps34 Mrps10 Sssca1 Atp5g1 Stoml2 Psmb3 Psmb5 Psmg1 Rps27l Mrpl28 Mrpl36 Mrpl22 Mrpl40 Mrpl11 Mrpl12 Mrpl24 Mrpl14 Mrpl54 Mrpl50 Mrpl45 Mrpl44 Mrpl16 Mrpl46 Grpel1 C1qbp Rpl7l1 Apex1 Naa10 Mrps7 Prmt3 Polr2f Emg1 Rpl27 Mrpl4 Mrpl2 Nhp2 Phb2 Qtrt1 Clpp 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE52542 [9] Only showingfirst200datasets-Seetxtoutputforfulldetails. GSE23833 [12] GSE27114 [6] GSE28389 [20] GSE46090 [12] GSE46606 [30] GSE20954 [14] GSE27092 [6] GSE38031 [8] GSE53951 [10] GSE56345 [9] GSE30160 [6] GSE13693 [9] GSE42238 [9] GSE10273 [9] GSE11973 [6] GSE11220 [44] GSE7275 [8] GSE46094 [10] GSE11222 [42] GSE20391 [11] GSE21944 [6] GSE18587 [9] GSE6196 [9] GSE13692 [8] GSE39458 [6] GSE38304 [8] GSE51608 [6] GSE12518 [6] GSE42883 [12] GSE56135 [8] GSE44923 [16] GSE5127 [18] GSE47872 [6] GSE41759 [14] GSE26616 [6] GSE35593 [6] GSE44175 [18] GSE31028 [6] GSE17728 [12] GSE25645 [17] GSE17709 [18] GSE32311 [11] GSE13547 [12] GSE26096 [10] GSE7759 [112] GSE40685 [11] GSE27379 [6] GSE22824 [24] GSE20987 [12] GSE46496 [9] GSE45968 [6] GSE8025 [21] GSE34961 [9] GSE13805 [7] GSE27811 [9] GSE15587 [6] GSE32277 [33] GSE7020 [8] GSE40230 [15] GSE10589 [6] GSE23040 [6] GSE31244 [6] GSE13611 [8] GSE10587 [6] GSE53077 [8] GSE25825 [8] GSE33121 [10] GSE25423 [10] GSE12464 [23] GSE16454 [24] GSE37907 [24] GSE7050 [18] GSE38538 [6] GSE21063 [24] GSE46091 [8] GSE51385 [8] GSE41942 [6] GSE27378 [8] GSE24061 [88] GSE14753 [6] GSE23408 [39] GSE8044 [6] GSE16925 [15] GSE45619 [6] GSE18135 [18] GSE34126 [19] GSE27605 [8] GSE58307 [20] GSE5976 [12] GSE55607 [18] GSE31598 [12] GSE17373 [24] GSE46797 [6] GSE7897 [60] GSE6998 [32] GSE21041 [6] GSE22180 [60] GSE55356 [6] GSE20500 [6] GSE31313 [22] GSE38693 [8] GSE33471 [12] GSE12498 [12] GSE33199 [64] GSE21299 [12] GSE17497 [10] GSE2527 [6] GSE18907 [12] GSE38277 [18] GSE6116 [70] GSE31570 [6] GSE36392 [9] GSE30746 [16] GSE39897 [36] GSE10912 [6] GSE6837 [8] GSE18042 [18] GSE8431 [12] GSE12499 [10] GSE9652 [11] GSE9441 [36] GSE56482 [8] GSE34065 [6] GSE54653 [6] GSE5035 [12] GSE7948 [13] GSE23101 [20] GSE8683 [11] GSE6030 [6] GSE59437 [30] GSE35543 [6] GSE21905 [6] GSE27816 [14] GSE54056 [12] GSE10365 [9] GSE30293 [8] GSE7381 [6] GSE38754 [40] GSE25778 [6] GSE39391 [21] GSE27786 [20] GSE15155 [12] GSE47414 [18] GSE36814 [20] GSE35785 [10] GSE47205 [10] GSE24628 [16] GSE5332 [12] GSE13408 [14] GSE6674 [15] GSE3554 [6] CEM+ CEM GSE13707 [20] GSE12049 [6] GSE15268 [16] GSE21900 [12] GSE36974 [14] GSE43899 [12] 0.0 GSE6933 [15] GSE35160 [6]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 130.87 131.10 131.29 132.14 132.29 133.42 134.16 134.73 134.90 135.45 135.88 136.46 139.33 142.37 143.32 143.91 144.09 144.87 145.21 145.48 146.78 146.96 149.72 150.03 150.10 150.94 155.14 156.68 157.51 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page2 Rps19bp1 Timm17a Samm50 Tomm22 Tomm20 Tomm40 Mrps18a Tmem11 Timm10 Ndufaf6 Chchd1 Ccdc58 Mrps12 Mrps22 Mrps16 Dctpp1 Psmb6 Psmb2 Psmg3 Psmb4 Psma7 Psmc4 Mrpl20 Mrpl34 Mrpl42 Mrpl13 Mrpl37 Mrpl18 Mrpl55 Polr2h Nop10 Wdr74 Wdr18 Nop16 Aimp2 Hspe1 Polr2j Banf1 Yars2 Nif3l1 Sf3b5 Emc6 Lsm4 Imp4 Mtx1 Adsl Eif3i Parl Fxn Uxt 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 112.49 112.61 112.88 113.31 113.34 113.41 113.43 113.68 113.76 114.12 114.43 114.47 114.54 115.89 116.77 117.36 117.38 117.43 117.78 118.26 119.06 119.21 120.04 120.17 120.18 120.27 120.33 120.50 120.72 120.77 121.48 121.64 122.13 124.10 124.28 125.24 125.59 125.84 125.98 126.16 126.47 126.58 127.16 127.45 127.89 129.04 129.76 130.32 130.47 130.84 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page3 BC003965 Aurkaip1 N6amt2 Exosc5 Mrps26 H2-Ke2 Ndufb6 Aarsd1 Malsu1 Ndufv2 Ruvbl2 Cmss1 Psma6 Mrpl10 Mrpl39 Mrpl27 Polr1d Polr2c Polr1c Wdr55 Cops6 Ddx39 Uqcc2 Eif1ad Cdc34 Ddx49 Ddx56 Dpy30 Znhit3 Snrpc Nudt1 Park7 Pold2 Bola2 Phf5a Nme1 Lsm2 Sdhd Pycrl Kti12 Eif3d Eif3g Hax1 Ece2 Txn2 Drg1 Slirp Cct5 Nip7 Eif3l 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 99.94 99.97 100.04 100.09 100.12 100.14 100.15 100.61 100.75 100.87 101.54 101.64 101.74 101.77 101.97 101.99 102.01 102.20 102.77 103.33 103.53 103.67 104.01 104.19 104.22 104.44 104.56 104.74 104.76 105.72 106.12 106.53 106.67 107.08 107.37 108.36 108.75 109.03 109.04 109.11 109.28 109.35 109.45 109.81 110.22 110.27 111.27 111.39 111.71 112.17 1.0 Notes 9430016H08Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page4 Ebna1bp2 Wbscr22 Tamm41 Timm8b Ranbp1 Chchd4 Exosc7 Dhrs7b Uqcr11 Ndufs7 Ndufs8 Ndufs3 Ruvbl1 Psmc3 Psma4 Mrpl47 Magoh Rangrf Gtf2h5 Grwd1 Nubp1 Polr1e Stra13 Aimp1 Cops5 Eif2b5 Eif2b1 Eif2b3 Naa38 Mrp63 Jagn1 Gtf2f2 Snrpb Prmt1 Polr2i Dus1l Trap1 Lsm3 Glrx3 Gtf3a Hint1 Coq7 Pno1 Coa7 Cyc1 Ppil1 Pes1 Gart Tbl3 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 93.23 93.38 93.48 93.55 93.60 93.78 93.90 94.03 94.19 94.23 94.28 94.31 94.32 94.37 94.52 94.64 94.65 94.65 94.95 95.30 95.32 96.09 96.27 96.28 96.61 96.69 96.75 96.91 97.25 97.25 97.32 97.49 97.58 97.59 97.66 98.00 98.50 98.73 98.89 98.94 99.27 99.39 99.41 99.49 99.54 99.70 99.74 99.80 99.81 99.91 1.0 Notes 1810009A15Rik 1110004E09Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page5 Tmem147 Xrcc6bp1 Fam195a Psmd12 Dnajc11 Uqcrfs1 Ndufaf2 Exosc3 Snrpd3 Ndufb5 Rnmtl1 Ndufa8 Ndufa9 Nudt21 Atad3a Pmpcb Psmg4 Eef1e1 Psma2 Mrpl41 Mrpl43 Mrpl23 Mrpl48 Prpf31 Nubp2 Rpp30 Cox5a Ahsa1 Thoc6 Sec13 Snrpg Rrp15 Hmbs Bccip Bcs1l Siva1 Snrpf Gpn1 Dohh Nop9 Dcps Tufm Ecsit Pus1 Mars Mecr Bysl Srm 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 85.07 85.19 85.24 85.29 85.52 85.53 85.53 85.60 85.68 85.87 85.90 85.97 86.11 86.11 86.16 86.53 86.54 86.63 86.68 87.15 87.24 88.40 88.53 88.55 88.59 88.62 88.78 88.95 88.96 89.19 89.29 89.53 89.60 89.65 89.78 90.11 90.11 90.28 90.63 90.80 90.87 90.89 90.92 91.18 91.62 91.85 91.88 92.08 92.97 93.02 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page6 Rnaseh2a Zmynd19 Ccdc124 Mrps18c Mmachc Snrnp40 Timm22 Exosc2 Mrps33 Ndufb7 Uqcrc1 Ndufv1 Atp5g2 Atp5a1 Suclg1 Psmb7 Psmc2 Psmc5 Mrpl32 Polr2d Cops4 Rpp40 Nedd8 Pa2g4 Prmt5 Atp5d Pfdn4 Pomp Cisd1 Nol12 Ptcd2 U2af1 Nme6 Noc4l Mrpl3 Taf10 Mbd3 Nob1 Coq3 Dap3 Rae1 Tefm Lap3 Drg2 Cct7 Ubl4 Cct2 Nifk Pdf Mif 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 77.71 77.88 78.03 78.17 78.18 78.25 78.37 78.41 78.62 78.84 78.90 79.18 79.51 79.56 79.62 79.81 79.88 80.02 80.12 80.13 80.14 80.26 80.26 80.46 80.69 81.46 81.61 81.83 82.01 82.06 82.15 82.23 82.36 82.37 82.56 82.66 82.71 82.71 82.81 82.83 82.85 83.01 83.29 83.43 83.50 83.89 83.92 84.06 84.46 85.00 1.0 Notes 9130401M01Rik 1110001J03Rik D17Wsu104e Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page7 Anapc15 Tmem97 Timm44 Poldip2 Csnk2b Tomm7 Mrps31 Mrps24 Spryd4 Ndufc1 Rbm8a Mthfd1 Psma1 Psmc1 Ptrhd1 Atp5f1 Nop56 Dtymk Cpsf3l Hddc2 Cops3 Haus1 Eif2b4 Lage3 Galk1 l7Rn6 Cct6a Txnl1 Lsm6 Tsta3 Myg1 Crls1 Coq6 Pop7 Ppa1 Imp3 Rrp9 Clpb Rcl1 Elp5 Gfer Mri1 Lias Mrrf Nit2 Fh1 Itpa 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 71.73 72.08 72.08 72.12 72.20 72.43 72.47 72.52 72.60 72.65 72.71 72.93 73.01 73.05 73.09 73.36 73.38 73.55 74.06 74.19 74.23 74.54 74.74 74.82 74.83 74.89 74.89 75.12 75.16 75.18 75.19 75.22 75.30 75.35 75.53 76.47 76.50 76.67 76.75 76.75 76.94 76.96 77.04 77.04 77.11 77.13 77.26 77.37 77.37 77.64 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page8 Tmem261 Mybbp1a Snrnp25 Dnajc15 Ndufaf1 Hspbp1 Prkrip1 Zc3hc1 Arl6ip4 Ptpmt1 Nudt19 Pmpca Psmd6 Rsl1d1 Psmd9 Mrpl52 Atpaf2 Atp5j2 Nup43 Shmt2 Cdc26 Asna1 Cd320 Cdc37 Tubg1 Eif4a1 Mrps9 Tsen2 Mettl1 Nudt2 Gins4 Abcf2 Bnip1 Nme2 Bola3 Eif3m Strap Gps1 Guk1 Ccnh Bop1 Coa3 Tcp1 Abt1 Rfc5 Rfc4 Snf8 Nxt1 Ppie Cs 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 65.78 65.90 66.00 66.09 66.17 66.19 66.29 66.37 66.45 66.81 67.01 67.04 67.24 67.29 67.30 67.58 67.69 67.71 67.95 67.98 68.02 68.14 68.38 68.44 68.48 68.59 68.66 68.67 68.68 68.70 68.77 69.02 69.05 69.08 69.24 69.56 69.57 69.67 69.94 69.99 69.99 70.00 70.00 70.19 70.33 70.47 70.60 70.88 70.92 71.58 1.0 Notes A430005L14Rik 0610009D07Rik 2700094K13Rik 2810428I15Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page9 Trnau1ap Ccdc101 Ndufb10 Ndufaf5 Sac3d1 Apopt1 Uqcrc2 Alkbh7 Psmd4 Ptges2 Mrpl49 Cirh1a Nsun2 Pbdc1 Pdcd2 Cks1b Ddx18 Actl6a Thoc3 Msto1 Mipep Atp5b Atp5h Nubpl Pfdn1 Xrcc6 Emc4 Sf3a3 Idh3g Elac2 Ttc27 Mdh2 Bzw2 Nop2 Pdhx Aven Stip1 Ppil3 Ppa2 Eif3k Ftsj1 Mtg1 Alg3 Ifrd2 Rfc3 Aprt 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 60.75 60.76 60.77 60.86 61.19 61.45 61.61 61.64 61.69 61.74 61.79 61.81 61.86 61.92 61.96 62.03 62.09 62.18 62.19 62.26 62.29 62.49 62.57 62.72 62.86 63.02 63.19 63.28 63.35 63.44 63.44 63.49 63.51 63.60 63.64 63.70 63.80 63.95 64.04 64.06 64.22 64.24 64.73 64.82 64.86 64.86 64.97 65.17 65.22 65.56 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page10 Hsd17b10 Commd2 Commd1 Wbscr16 Rsl24d1 Fam96a Ndufaf4 Prpf38a Abhd11 Cops7a Mrps36 Arpp19 Ndufb9 Atp5c1 Pgam5 Psmd8 Polr2g Slmo2 Ddx27 Gpr89 Mettl5 Gmps Rrp12 Gins1 Gins2 Pfdn2 Smn1 Rpl14 Smu1 Tars2 Lsm1 Glrx5 Gpn2 Ngdn Nans Noa1 Acn9 Ppan Rpa2 Rpa3 Elof1 Nelfe Lsg1 Nfu1 Cct4 Dnlz Taf9 Isy1 Aatf Atic 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 55.61 55.64 55.84 55.93 56.02 56.12 56.39 56.56 56.74 56.80 56.89 57.03 57.15 57.16 57.29 57.30 57.33 57.57 57.65 57.81 57.82 57.84 57.94 58.07 58.26 58.35 58.40 58.57 58.92 58.92 58.95 58.99 59.21 59.31 59.31 59.71 59.80 59.81 59.86 59.94 59.95 60.03 60.18 60.25 60.37 60.44 60.49 60.55 60.57 60.65 1.0 Notes 2700060E02Rik 1700021F05Rik 1110008F13Rik 1110004F10Rik 3110082I17Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page11 Cdk2ap1 Hnrnpab Magohb Fam58b Ctnnbl1 Tsen15 Akr1b3 Ndufa5 Ndufa4 Ndufa7 Higd1a Pdcd2l Psmd3 Adrm1 Bri3bp Polr3h Dnph1 Nup35 Nup85 Spag7 Pdap1 Usp39 Gmnn Alyref Mcm7 Noc2l Nol11 Ptcd3 Taf12 Plrg1 Wdr4 Eif3b Rcc1 Fen1 Gars Mtx2 Yrdc Rtcb Ssr2 Rpl8 Tsr2 Lyar Ppif Ak2 Bax 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 50.52 50.55 50.55 50.56 50.61 50.70 50.71 50.78 50.79 50.82 50.95 50.97 51.07 51.18 51.33 51.37 51.45 51.50 51.82 51.92 52.04 52.42 52.46 52.46 52.63 52.70 53.04 53.12 53.15 53.38 53.39 53.55 53.60 53.69 53.77 53.81 53.84 53.86 53.89 54.07 54.09 54.11 54.42 54.47 54.88 54.94 54.99 55.09 55.25 55.28 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page12 Tmem126a Rnaseh2c Tmem14c Nr2c2ap Psmd14 Oxnad1 Gemin2 Cdc123 Cox7a2 Mrps21 Ndufb3 Snrpa1 Ppp1r7 Chrac1 Pradc1 Dcaf13 Wdr73 Nup93 Cox18 Ube2k Znhit1 Arfrp1 Vdac2 Naa20 Echs1 Thoc5 Tceb2 Mcm5 Rrp36 Gspt1 Prdx3 Dars2 Mrpl9 Paics Pwp1 Pyurf Dhps Sod2 Shq1 Psph Ddx1 Ldha Tipin Ftsj3 Mcat Rars Ctu2 Ufc1 Ipo5 Ltv1 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 45.51 45.58 45.61 45.65 45.65 45.76 45.80 45.88 45.89 45.99 46.19 46.20 46.25 46.26 46.50 46.54 46.69 47.24 47.25 47.26 47.41 47.43 47.43 47.47 47.72 47.81 47.86 47.99 47.99 48.20 48.34 48.38 48.41 48.48 48.53 48.61 48.85 48.86 48.89 48.94 48.97 49.34 49.58 49.59 49.63 49.87 50.02 50.10 50.17 50.20 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page13 Tmem199 Rabggtb Sigmar1 Smim12 Slc25a5 Rbmxl1 Mrps25 Tarbp2 Rbm19 Rpp25l Psmd5 Psmd2 Cenpw Polr1b Med11 Nufip1 Nup62 Wdr36 Ncbp1 Nsfl1c Dynll2 Pebp1 Ppp5c Snrpe Adat2 Atp5k Pycr2 Szrd1 Uchl5 Apoo Coq4 Atp5j Ufm1 Yif1b Sdhc Cycs Pcna Lipt2 Hdgf Cluh Utp6 Ppat Hat1 Pgls Nle1 Faf1 Tpi1 Ung Etfb Spr 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 38.58 38.70 38.71 39.05 39.22 39.27 39.35 39.42 39.44 39.63 39.71 39.79 39.93 40.04 40.12 40.18 40.25 40.42 40.52 40.61 40.70 40.79 40.90 41.22 41.42 41.45 41.59 41.60 41.75 41.79 41.84 42.15 42.27 42.30 42.32 42.65 42.72 42.76 43.16 43.47 43.51 43.81 43.89 44.36 44.49 44.57 44.66 44.72 44.99 45.37 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page14 Tomm70a Tmem208 Ccdc115 Psmc3ip Dnajc24 Fastkd5 Gemin5 Nudcd2 Tubb4b U2af1l4 Ppp1r8 Atp5g3 Sdhaf1 Suclg2 Smyd2 Smyd5 Pam16 G3bp1 Med27 Med21 Osgep Apitd1 Wdr46 Cox10 Hspa9 Ddx41 Dtwd1 Spc24 Fkbp3 Mrps2 Cnih4 Dimt1 Trmt5 Nat10 Nmt1 Rad1 Dkc1 Acy1 Yif1a Naca Aaas Qdpr Mto1 Orc6 Rrp8 Rrs1 Mzt2 Rfc2 Aen Ilf2 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 35.41 35.55 35.60 35.66 35.68 35.72 35.74 35.83 35.83 35.85 35.92 36.17 36.26 36.28 36.30 36.48 36.49 36.50 36.51 36.66 36.71 36.73 36.74 36.74 36.78 36.88 36.92 36.96 36.98 37.08 37.18 37.20 37.26 37.37 37.66 37.73 37.79 37.79 37.91 38.01 38.03 38.09 38.19 38.24 38.34 38.44 38.46 38.48 38.53 38.53 1.0 Notes 2010107E04Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page15 Nsmce4a Timm17b Tmem70 Zswim7 Enoph1 Nudcd1 Cacybp Cox6b1 Nup133 Ncaph2 Ppp1ca Tbc1d7 Cnot11 Ndufs2 Dnaaf2 Alkbh2 Rnf126 Ppm1g Eefsec Cwc15 Dhodh Mak16 Polr3c Trip13 Ddx28 Cox19 Ppp4c Lonp1 Ssna1 Vdac1 Mcm2 Gnb1l Nudt8 Cpsf3 Grhpr Phpt1 Znrd1 Rpl7a Mtfp1 Atp5l Nudc Tfam Got2 Dctd Yars Rtca Pstk Tars Tk1 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 30.49 30.58 30.58 30.77 30.84 30.98 31.16 31.21 31.23 31.34 31.40 31.45 31.63 31.77 32.02 32.08 32.22 32.23 32.25 32.25 32.46 32.56 33.04 33.23 33.33 33.51 33.57 33.69 33.82 33.98 34.03 34.18 34.25 34.29 34.34 34.41 34.50 34.50 34.54 34.54 34.89 34.93 34.95 35.01 35.06 35.11 35.21 35.27 35.30 35.37 1.0 Notes 2310039H08Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page16 Mphosph6 Babam1 Fam96b Slc35a4 Bckdhb Nup107 Sec61b Mettl22 Mad2l2 Chmp6 Romo1 Chaf1b Gm561 Gtf2h3 Armc6 Endog Atpaf1 Lrrc59 Polr1a Cops8 Ddx51 Usp10 Tfb1m Vps29 Eif2s2 Cfdp1 Prim1 Rars2 Trub1 Trmt1 Asf1a Cse1l Pole2 Pwp2 Mnd1 Gpn3 Gfm2 Tyw3 Blmh Deb1 Sco2 Eif3c Eif5a Immt Tdp1 Dars Cuta Rpl6 Tsr3 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 24.49 24.52 24.53 24.60 24.64 24.75 24.75 24.84 24.91 25.06 25.38 25.39 25.47 25.49 25.86 25.97 26.02 26.03 26.25 26.33 26.41 26.43 26.54 26.65 26.71 26.75 26.83 26.90 26.97 27.08 27.15 27.26 27.81 27.92 28.21 28.29 28.66 28.68 28.72 29.10 29.12 29.37 29.53 29.67 29.84 30.13 30.13 30.18 30.32 30.47 1.0 Notes 1110008L16Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page17 Cdkn2aipnl D2Wsu81e AU022252 Tmem242 Tmem238 Tomm40l Fam203a Eif4ebp1 Snrnp27 Lamtor5 Foxred1 Slc19a1 Krtcap2 Comtd1 Immp1l Gtf2e2 Heatr3 Rqcd1 Ubxn1 Bckdk Cdc45 Rad51 Rps19 Poc1a Syce2 Apool Prps1 Parp1 Tbrg4 Ears2 Xrcc5 Sfxn1 Riok2 Nme4 Pinx1 Taf11 Mogs Cnbp Srsf9 Cope Wdr5 Pdhb Pgk1 Hars Ctps Sars Dis3 Ydjc Eci1 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 20.71 20.82 20.90 21.11 21.12 21.14 21.21 21.24 21.24 21.26 21.49 21.71 21.73 21.74 21.77 21.79 21.94 22.02 22.13 22.15 22.26 22.29 22.30 22.37 22.46 22.57 22.73 22.75 22.81 22.85 22.86 22.95 23.12 23.13 23.17 23.44 23.50 23.58 23.60 23.60 23.61 23.68 23.70 23.85 24.14 24.14 24.30 24.33 24.44 24.46 1.0 Notes Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page18 Rnaseh2b Hsp90ab1 Pla2g12a Nudt16l1 Mmadhc Trmt10c Smim11 Pak1ip1 Timm21 Mterfd2 Pdcd11 Metap2 Mettl13 Ndufa2 Dmap1 Pgam1 Ino80e Srfbp1 Gtf2h2 Heatr1 Diablo Wdr43 Haus4 Lrwd1 Impa2 Gtf2f1 Hirip3 Aifm1 Trmt6 Ciao1 Tcof1 Mkks Coq9 Rpa1 Eif3h Uba2 Fdps Ftsj2 Urod Manf Rrn3 Gnl3 Cdt1 Dtd1 Hn1l Lzic Hn1 Dlat Mpi Ddt 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 16.31 16.37 16.43 16.52 16.54 16.58 16.59 16.65 16.76 16.76 16.80 16.82 17.41 17.42 17.43 17.55 17.78 17.83 17.88 17.96 18.08 18.16 18.28 18.29 18.41 18.48 18.52 18.54 18.60 18.87 18.92 19.04 19.11 19.13 19.23 19.29 19.59 19.61 19.67 19.75 19.81 19.83 19.86 19.88 19.96 20.03 20.38 20.38 20.50 20.64 1.0 Notes 2310009B15Rik 2210016F16Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page19 Tmem192 Rnaseh1 Fam98a Chchd6 Anp32b Nup155 Tysnd1 Mcmbp Uqcr10 Cenpm Ndufs1 Usmg5 Rpl13a Pet112 Gmpr2 Tm2d3 Med30 Nop58 Cenpv Triap1 Abce1 Rexo2 Ap1s1 Cdc20 Hspa4 Ap3s2 Pcbp1 Uqcrb Mcm6 Cdpf1 Ssrp1 Prim2 Utp15 Rplp0 Stub1 Wipi2 Nthl1 Cstf2 Exo1 Ybx1 Lipt1 Tbcb Toe1 Got1 Alg5 Tsr1 Pigf Ncl 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 12.45 12.48 12.51 12.62 12.63 13.17 13.19 13.22 13.22 13.24 13.25 13.32 13.38 13.41 13.43 13.58 13.63 13.87 13.89 13.91 14.03 14.06 14.20 14.37 14.39 14.52 14.60 14.65 14.73 14.74 14.81 14.93 14.95 14.95 15.00 15.01 15.02 15.23 15.24 15.29 15.35 15.37 15.37 15.58 15.59 15.61 15.69 15.76 16.00 16.29 1.0 Notes 2310011J03Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page20 BC055324 Thumpd3 Fam105b Txndc17 Gpatch4 Lamtor1 Adprhl2 Ndufaf7 Top1mt Pabpc4 Zdhhc6 Bcl2l13 Yae1d1 Pdzd11 Gtpbp4 Hnrnpf Lrpprc Cenpp Hdhd2 Afg3l2 Wdr83 Nup88 Lyrm4 Ddx47 Cdca7 Znhit6 Mnat1 Dhrs4 Nudt9 Srp19 Ube2t Ercc1 Tfdp1 Pole3 Flad1 Pop1 Rps2 Eno1 Cdk1 Pop4 Pdxk Cks2 Orc3 Dera Vars Pfas Hprt Etfa Tfpt 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 9.48 9.48 9.57 9.63 9.69 9.72 9.76 9.84 9.85 9.91 9.94 9.96 9.96 10.00 10.02 10.13 10.16 10.16 10.21 10.23 10.38 10.41 10.56 10.60 10.70 10.71 10.77 10.80 10.87 10.91 10.96 11.03 11.08 11.14 11.17 11.71 11.72 11.72 11.77 11.78 11.84 11.87 11.94 12.09 12.14 12.15 12.27 12.31 12.39 12.43 1.0 Notes 2410016O06Rik 1810043H04Rik 0610007P14Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page21 Aasdhppt Thumpd1 Slc25a26 Ube2cbp Ankrd39 Lamtor2 Mvb12a Wrap53 Psmd1 Cbwd1 Tmed1 Cenph Phgdh Ergic1 Kpna2 Cox6c Ccne1 Ssbp1 Sdf2l1 Ubac1 Vdac3 Skp1a Naa25 Zmat5 Mrps6 Mcrs1 Tex30 Aurka Glod4 Nars2 Prdx2 Metrn Lsm7 Bzw1 Birc5 Bod1 Coq5 Rps5 Rcc2 Taf5l Mlh1 Utp3 Nt5c Elp3 Gtl3 Ttf2 Iars 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 5.91 6.10 6.18 6.24 6.31 6.34 6.38 6.63 6.64 6.68 6.74 6.78 6.82 6.82 6.93 6.95 6.97 6.99 7.05 7.15 7.31 7.32 7.42 7.59 7.59 7.60 7.87 8.00 8.09 8.20 8.21 8.22 8.23 8.27 8.28 8.29 8.29 8.33 8.66 8.72 8.75 8.79 8.83 8.89 9.09 9.11 9.12 9.13 9.30 9.47 1.0 Notes C230052I12Rik 2310061I04Rik Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page22 Fam173b Slc25a13 Snrnp35 Ndufab1 Ndufb11 Mpv17l2 Trmt61a Mthfd1l Dazap1 Otud6b Akr7a5 Trmt2a Cox4i1 Rpl10a Spata5 Isyna1 Brms1 Chtf18 Nelfcd Abcb8 Cox11 Ddx20 Cdca5 Lcmt1 Fkbp2 Mcts1 Cpsf4 Rplp2 Chd1l Avpi1 Vwa9 Surf6 Gcdh Med4 Htra2 Tyw1 Odc1 Dpcd Clybl Pmf1 Kif22 Bag2 Peo1 Apip Lars Ttc1 Dlst Set 0.0 1.0

GSE48397 [10] GSE16874 [12]

GSE5891 [6] Scale ofaveragePearsoncorrelations GSE48203 [9] GSE42299 [8] GSE38257 [14] GSE6881 [10] GSE43779 [6] GSE19474 [12] 0.2 GSE21278 [48] GSE42021 [27] GSE25252 [10] GSE30012 [6] GSE9355 [51] GSE35998 [20] GSE3313 [24] GSE33761 [9] GSE15267 [8] 0.4 GSE15808 [29] GSE55525 [71] GSE24789 [9] GSE17462 [8] GSE43197 [27] GSE1871 [12] GSE31702 [10] GSE13302 [30] GSE27329 [24] 0.6 GSE7460 [52] GSE22989 [10] GSE19954 [8] GSE40282 [6] GSE34279 [30] GSE48204 [6] GSE46211 [18] GSE51080 [18] GSE15541 [12] 0.8 GSE32615 [10] GSE8684 [10] GSE46723 [6] GSE11572 [12] Score 2.61 2.65 2.68 2.76 2.83 2.84 2.90 2.93 3.08 3.08 3.11 3.17 3.26 3.31 3.40 3.41 3.45 3.54 3.58 3.67 3.68 3.69 3.74 3.78 3.86 3.88 3.94 4.02 4.06 4.27 4.29 4.43 4.50 4.51 4.59 4.61 4.65 4.69 4.85 4.89 5.16 5.25 5.27 5.44 5.48 5.50 5.83 5.89 5.90 5.91 1.0 Notes E130309D02Rik Mphosph10 Symbol Num ofCEMGenes:21.Predicted1106.SelectedDatasets:339.Strength:26.1 CEM 1,Geneset"[G]ribosome",Page23 Bloc1s2 L3mbtl2 Gmppb Tsen54 Recql4 Pitpnb Nup54 Acbd6 Enkd1 Usp14 Cdca4 Znhit2 Gnpat Mcts2 Gsto1 Cnih1 Dctn3 Clhc1 Puf60 Pus7l Eme1 Coq2 Bag1 Pus7 Ift27 0.0 1.0

GSE48397 [10] GSE16874 [12]

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

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

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

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

0.754 Kernel fit Pairwise Correlations Normal fit

Density 0.377

0.000 CEM 1

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

Pre-normalization Quantiles

lung fibroblasts,lung fibroblasts,lung biological fibroblasts,lung biological fibroblasts,replicatelung biological fibroblasts,replicate 1carcinoma-asssociated (0.0806952) biological replicate 2carcinoma-asssociated (0.138003) biological replicate 3carcinoma-asssociated (0.278529) replicate 4carcinoma-asssociated (0.172022)fibroblasts, 5carcinoma-asssociated (0.0507818)fibroblasts, biological fibroblasts, biological fibroblasts,replicate biological fibroblasts,replicate 1 (0.0437396) biological[ replicate min2 (0.0277283) biological replicate 3 ](0.082403) replicate 4 (0.0728767) [5 (0.053221)medium ] [ max ] CEM 1 Mrpl2 1853.4 2377.9 3380.6 P ( S | Z, I ) = 1.00 Mrps10 1061.4 2349.7 3522.0 Mean Corr = 0.88821 Mrpl46 627.8 862.8 1865.6 Mrps34 1681.0 2315.4 3247.6 Mrpl16 1122.4 1906.0 3514.2 Mrps23 824.5 1270.7 2590.9 Mrpl44 373.5 574.8 813.0 Mrps30 997.9 1370.3 2106.7 Apex1 1514.4 2854.8 5016.8 Mrps27 264.8 339.0 710.6 Mrpl45 1537.2 1945.0 2527.8 Rpl7l1 1229.0 1656.6 2752.4 Mrpl4 1303.8 1577.6 2299.1 Mrpl50 705.4 1131.7 1540.9 Mrpl54 1041.7 1234.9 2834.1 Rps27l 10658.8 11096.8 15646.6 Qtrt1 450.0 685.8 1133.0 Mrpl14 1255.3 1466.1 3461.9 Rpl27 13734.9 15935.8 18634.5 Mrpl24 2121.3 2531.7 4375.0 Prmt3 1023.4 1765.1 2172.2 Mrpl12 1283.2 2643.5 8208.8 Stoml2 753.2 1011.9 2438.3 Timm13 4171.3 5514.8 10386.2 Clpp 1743.6 2580.3 3412.2 Mrps7 1367.7 2129.0 3321.7 CEM 1 + Mrpl11 1610.5 1980.0 4307.3 Top 10 Genes Exosc4 839.2 1253.3 2068.3 C1qbp 3192.5 5246.9 6748.2 Phb2 2242.8 2912.7 5234.0 Naa10 463.1 953.0 2343.8

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE16874" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 12 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16874 Status: Public on Dec 07 2010 Title: Expression in wild type and TgDREAM mouse B cells unstimulated or 2 days after LPS+IL4 stimulation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21059893 Summary & Design: Summary: DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two proteins related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.

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

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

0.423 Kernel fit Pairwise Correlations Normal fit

Density 0.212

0.000 CEM 1

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

Pre-normalization Quantiles

BCells_WildType_day0_REP1BCells_WildType_day0_REP2BCells_WildType_day0_REP3BCells_Transgenic_day0_REP1 BCells_Transgenic_day0_REP2(0.0972903) BCells_Transgenic_day0_REP3(0.0784988) BCells_WildType_day2_REP1(0.0675435)BCells_WildType_day2_REP2 (0.0809102)BCells_WildType_day2_REP3 (0.0825318)BCells_Transgenic_day2_REP1 (0.096099) BCells_Transgenic_day2_REP2(0.0851625) BCells_Transgenic_day2_REP3(0.0790308) (0.117551) (0.065887) (0.0566552)[ (0.0928401)min ] [ medium ] [ max ] CEM 1 Mrpl2 964.3 2551.4 3139.6 P ( S | Z, I ) = 1.00 Mrps10 378.1 1425.3 1904.7 Mean Corr = 0.88425 Mrpl46 907.3 2808.0 3295.7 Mrps34 1195.4 3320.3 3785.8 Mrpl16 1180.7 2696.9 3075.0 Mrps23 440.4 1036.2 1494.4 Mrpl44 356.0 966.8 1156.3 Mrps30 1012.2 2124.8 2235.5 Apex1 1272.4 6406.6 7918.4 Mrps27 356.0 570.9 680.8 Mrpl45 692.6 1847.0 2463.3 Rpl7l1 628.5 3025.9 3399.2 Mrpl4 1180.7 2659.8 3227.9 Mrpl50 435.1 845.2 1346.8 Mrpl54 582.2 1165.8 1547.1 Rps27l 2390.8 10849.6 12645.9 Qtrt1 768.1 1190.3 1559.0 Mrpl14 577.1 790.7 1020.7 Rpl27 17715.3 24104.6 25644.8 Mrpl24 2516.3 2882.9 3227.9 Prmt3 846.4 1523.5 2196.5 Mrpl12 1107.2 4411.6 5738.2 Stoml2 845.3 2910.6 3329.3 Timm13 1891.7 4827.6 5583.8 Clpp 762.9 1637.3 2142.9 Mrps7 998.3 2984.2 3757.0 CEM 1 + Mrpl11 1363.7 2516.3 3181.2 Top 10 Genes Exosc4 324.6 788.6 1109.2 C1qbp 2098.9 11772.6 14129.1 Phb2 2907.2 7985.4 10560.4 Naa10 817.7 2175.4 2638.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE52542" 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=GSE52542 Status: Public on Nov 21 2013 Title: VEGF Isoform Transcriptome Changes in the E9.5 Murine Forebrain Organism: Mus musculus Experiment type: Third-party reanalysis Platform: GPL1261 Pubmed ID: 24124161 Summary & Design: Summary: Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice.

Overall design: This study comprises of new samples and reanalysis of Samples from GSE30767 and GSE8091.

Background corr dist: KL-Divergence = 0.0176, L1-Distance = 0.0390, L2-Distance = 0.0022, Normal std = 0.7805

0.511 Kernel fit Pairwise Correlations Normal fit

Density 0.256

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

forebrain_Vegf188_1forebrain_Vegf188_2forebrain_Vegf188_3 (0.116881)forebrain_Vegf188_4 (0.156434)forebrain_wildtype_5 (0.0851069)forebrain_wildtype_6 (0.1624)forebrain_Vegf120188_1 (0.105596)forebrain_Vegf120188_2 (0.121872)forebrain_Vegf120188_3 (0.084419) (0.0798421) (0.0874495)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1380.5 1776.6 2191.1 P ( S | Z, I ) = 1.00 Mrps10 977.3 1517.6 1928.1 Mean Corr = 0.86768 Mrpl46 939.1 1042.9 1538.7 Mrps34 976.6 1349.2 2857.6 Mrpl16 1491.3 1567.8 1958.1 Mrps23 415.8 694.7 1044.0 Mrpl44 528.4 711.8 995.3 Mrps30 1183.0 1249.3 1830.1 Apex1 4702.5 5563.5 7788.2 Mrps27 439.1 520.5 1042.9 Mrpl45 1211.8 1551.9 1891.5 Rpl7l1 1385.3 1544.7 2587.8 Mrpl4 1088.3 1447.7 2365.8 Mrpl50 564.8 763.4 1779.3 Mrpl54 797.7 1312.0 1865.7 Rps27l 12132.8 14994.8 18629.8 Qtrt1 491.5 603.8 941.4 Mrpl14 398.1 562.1 1371.7 Rpl27 11563.8 13579.4 22522.8 Mrpl24 1532.0 1756.9 2627.8 Prmt3 2058.8 2244.6 2792.9 Mrpl12 3244.9 4121.3 6757.8 Stoml2 1546.8 1965.2 3824.1 Timm13 1698.9 2894.7 5509.8 Clpp 650.5 883.4 1825.0 Mrps7 757.1 1184.5 1748.6 CEM 1 + Mrpl11 2160.8 2290.2 3656.5 Top 10 Genes Exosc4 340.2 423.3 1406.4 C1qbp 4775.7 6386.9 7674.0 Phb2 3844.5 5763.6 7520.5 Naa10 887.7 1055.4 1994.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE23833" 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=GSE23833 Status: Public on Sep 01 2010 Title: The Forkhead factor FoxQ1 influences epithelial differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20717954 Summary & Design: Summary: The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration and differentiation.In this study we identified the Forkhead factor FoxQ1 as increased in expression during TGF-beta1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity.The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts and an increased expression of several junction proteins (e.g. E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression.Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells.Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-beta1 induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, e.g. Ets-1, Zeb1 and Zeb2.In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation

Overall design:

Background corr dist: KL-Divergence = 0.0453, L1-Distance = 0.0772, L2-Distance = 0.0080, Normal std = 0.6930

0.668 Kernel fit Pairwise Correlations Normal fit

Density 0.334

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

2h_co._enriched12h_co._enriched22h_co._enriched3 (0.0918054)2h_co._total1 (0.0608542)2h_co._total2 (0.0796795) (0.0766916)2h_co._total3 (0.0415536)2h_TGFbeta_enriched1 (0.156129)2h_TGFbeta_enriched22h_TGFbeta_enriched32h_TGFbeta_total1 (0.121362)2h_TGFbeta_total2 (0.079111)2h_TGFbeta_total3 (0.0739431) (0.0699938) (0.0568163) (0.0920611)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 576.5 2092.4 2884.2 P ( S | Z, I ) = 1.00 Mrps10 569.9 1029.8 1259.3 Mean Corr = 0.85768 Mrpl46 778.1 1422.3 2041.3 Mrps34 496.2 1963.6 2475.8 Mrpl16 1111.6 2877.4 3425.9 Mrps23 92.6 325.5 394.7 Mrpl44 409.5 469.7 605.5 Mrps30 946.9 1488.5 2046.5 Apex1 2425.4 4508.3 5285.7 Mrps27 192.8 444.7 505.9 Mrpl45 509.3 1033.8 1582.1 Rpl7l1 1394.1 2193.9 2461.6 Mrpl4 272.4 1747.6 1880.7 Mrpl50 361.5 541.6 696.3 Mrpl54 124.9 348.9 424.5 Rps27l 2623.2 6555.0 7319.5 Qtrt1 593.6 1362.6 1783.1 Mrpl14 194.6 333.1 627.7 Rpl27 2724.9 7917.7 11097.1 Mrpl24 1206.5 3040.1 3657.9 Prmt3 1729.8 2761.9 3260.5 Mrpl12 642.5 2125.4 2684.6 Stoml2 463.5 1242.0 1383.7 Timm13 686.6 3417.1 5229.0 Clpp 590.9 1660.4 2085.4 Mrps7 595.2 1699.5 2381.4 CEM 1 + Mrpl11 1232.4 3999.2 5353.0 Top 10 Genes Exosc4 248.8 647.4 912.6 C1qbp 1788.6 8074.8 10490.8 Phb2 1008.1 4307.0 5795.3 Naa10 219.8 707.3 1116.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE27114" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.478 Kernel fit Pairwise Correlations Normal fit

Density 0.239

0.000 CEM 1

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

Pre-normalization Quantiles

2_ESwt_a2_ESwt_b (0.169227)2_NPwt_a (0.211688)2_NPwt_b (0.0672245)2_TNwt_a (0.0835095)2_TNwt_b (0.227799) (0.240552) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 1060.1 3120.1 4863.7 P ( S | Z, I ) = 1.00 Mrps10 857.9 2208.8 3623.2 Mean Corr = 0.84462 Mrpl46 986.0 1493.8 1683.7 Mrps34 1528.2 2446.8 2902.2 Mrpl16 1503.3 1761.2 2631.8 Mrps23 470.1 1379.3 1469.8 Mrpl44 351.7 1194.2 1288.2 Mrps30 577.4 1826.8 2049.6 Apex1 2502.0 7602.4 7698.5 Mrps27 391.2 779.7 1313.8 Mrpl45 1055.3 3138.2 4516.1 Rpl7l1 520.3 2776.1 3937.9 Mrpl4 1368.6 2134.3 2673.1 Mrpl50 784.1 1778.7 1927.8 Mrpl54 452.3 667.5 911.3 Rps27l 1638.8 10922.7 15638.3 Qtrt1 765.6 1593.0 2014.5 Mrpl14 789.3 1155.7 1699.0 Rpl27 14852.4 24701.9 27042.2 Mrpl24 1643.1 4870.1 7891.3 Prmt3 734.8 1635.6 2842.7 Mrpl12 2127.2 4119.1 4664.1 Stoml2 802.1 3196.2 3527.2 Timm13 3954.9 6990.2 7401.8 Clpp 1625.1 2812.4 3366.8 Mrps7 1081.9 1606.3 1779.1 CEM 1 + Mrpl11 1737.5 4131.4 4418.9 Top 10 Genes Exosc4 528.9 1250.7 1689.4 C1qbp 2332.0 6117.7 8865.8 Phb2 3769.5 7927.0 8527.4 Naa10 768.6 2172.3 2385.4

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE28389" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 20 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.705 Kernel fit Pairwise Correlations Normal fit

Density 0.353

0.000 CEM 1

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

Pre-normalization Quantiles

[E-MTAB-368][E-MTAB-368] Mouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMouse[E-MTAB-368] developmentalMousestage[E-MTAB-368] E7.5 developmentalMousestage[E-MTAB-368] 1 (0.112667) E7.5 developmentalMousestage[E-MTAB-368] 2 (0.0652309) E7.5 developmentalMousestage[E-MTAB-368] 3 (0.0900952) E8.5 developmentalMousestage[E-MTAB-368] 1 (0.0430205) E8.5 developmentalMousestage[E-MTAB-368] 2 (0.0261723) E8.5 developmentalMousestage[E-MTAB-368] 3 (0.0321579) E9.5 developmentalMousestage[E-MTAB-368] 1 (0.0397765) E9.5 developmentalMousestage[E-MTAB-368] 2 (0.0404909) E9.5 developmentalMousestage[E-MTAB-368] 3 (0.0366215) E10.5 developmentalMousestage[E-MTAB-368] 1 E10.5 (0.0309793) developmentalMousestage[E-MTAB-368] 2 E10.5 (0.0233362) developmentalMousestage[E-MTAB-368] 3 E12.5 (0.0383832) developmentalMousestage[E-MTAB-368] 1 E12.5 (0.0480105) developmentalMousestage[E-MTAB-368] 2 E14.5 (0.0440705) developmentalMousestage 1 E14.5 (0.0663433) developmentalMousestage 2 E16.5 (0.0459373) developmentalstage 1 E16.5(0.0389283) stage[ min 2 E18.5(0.0529138) stage 1] E18.5(0.0622318) 2 (0.0626328)[ medium ] [ max ] CEM 1 Mrpl2 1210.1 2240.4 3364.9 P ( S | Z, I ) = 1.00 Mrps10 803.3 1554.6 2070.9 Mean Corr = 0.84448 Mrpl46 908.7 1866.6 2950.2 Mrps34 1360.8 3661.1 5704.7 Mrpl16 1595.0 2883.1 3926.4 Mrps23 966.3 1514.6 2188.5 Mrpl44 517.4 912.3 1352.2 Mrps30 807.2 1996.2 2769.4 Apex1 2446.6 9467.6 11811.0 Mrps27 367.6 734.0 1193.2 Mrpl45 1030.6 2180.9 2944.9 Rpl7l1 1743.6 3484.0 5084.9 Mrpl4 984.7 2131.7 3127.3 Mrpl50 1652.2 2109.5 2482.8 Mrpl54 855.8 1225.3 1506.5 Rps27l 6258.7 11622.1 15654.0 Qtrt1 322.8 1090.6 1897.5 Mrpl14 1005.2 1261.8 1688.9 Rpl27 14705.4 33554.2 41534.2 Mrpl24 2601.9 3617.0 4888.3 Prmt3 1117.3 1912.5 3544.1 Mrpl12 2602.8 4857.0 8997.4 Stoml2 1352.2 3167.1 4508.1 Timm13 2432.8 5650.6 8101.7 Clpp 1291.4 2402.7 3340.3 Mrps7 1351.5 1844.9 2664.1 CEM 1 + Mrpl11 1709.2 4222.9 5244.7 Top 10 Genes Exosc4 534.8 1489.9 1799.2 C1qbp 2964.9 7912.0 13305.5 Phb2 3059.5 7758.1 10860.2 Naa10 855.3 2400.4 3266.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE46090" 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=GSE46090 Status: Public on Apr 17 2013 Title: Gene expression in WT and Ikaros-deficient DN3, DN4 and DP thymocyte populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24643801 Summary & Design: Summary: DN3, DN4 and DP cells were sorted from 3-4 week old WT and mice and subjected to transcriptome analysis

Overall design: Cells from 3 mice were pooled for sorting.

Background corr dist: KL-Divergence = 0.0692, L1-Distance = 0.0334, L2-Distance = 0.0015, Normal std = 0.5233

0.791 Kernel fit Pairwise Correlations Normal fit

Density 0.396

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 DN3WT cells DN3 repWT cells 1 DN4 (0.0663272) repWT cells 2 DN4 (0.0651983) repWT cells 1 DP (0.0959423) rep cellsWT 2 DP (0.122463)rep cellsDN3 1 (0.14569) cellsrepDN3 2 rep (0.116526) cells 1DN4 (0.0360503) rep cells 2DN4 (0.0639627) rep cells 1DP (0.0577454) rep cells 2DP (0.0505964)rep cells 1 (0.0940371) rep 2 (0.0854607) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 1311.7 3620.7 4372.3 P ( S | Z, I ) = 1.00 Mrps10 341.4 1224.8 1631.3 Mean Corr = 0.82445 Mrpl46 1023.0 2143.2 2936.4 Mrps34 1085.0 2873.8 3486.3 Mrpl16 747.6 1878.4 2326.3 Mrps23 119.9 252.6 449.2 Mrpl44 446.4 687.7 940.9 Mrps30 1376.6 2376.8 2866.6 Apex1 479.1 4586.4 5222.3 Mrps27 283.9 923.9 1235.6 Mrpl45 719.2 1296.9 1866.5 Rpl7l1 478.1 1477.9 1775.8 Mrpl4 1274.4 2462.0 3482.2 Mrpl50 267.2 668.1 1045.6 Mrpl54 159.9 338.1 597.6 Rps27l 2232.4 5982.0 7028.3 Qtrt1 301.9 1136.0 1718.9 Mrpl14 335.5 628.2 857.0 Rpl27 15025.9 19918.6 21828.7 Mrpl24 4737.8 5886.7 6788.2 Prmt3 1086.5 3605.7 4496.6 Mrpl12 1198.4 3742.1 5370.2 Stoml2 478.8 1982.1 2177.8 Timm13 2074.9 4455.1 5365.1 Clpp 539.7 1197.3 1846.4 Mrps7 647.6 1390.1 2102.6 CEM 1 + Mrpl11 1530.3 3948.9 4777.9 Top 10 Genes Exosc4 622.0 998.3 1467.4 C1qbp 1396.5 10295.5 11383.1 Phb2 1872.3 5753.9 7269.5 Naa10 583.9 1383.2 2163.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE46606" 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=GSE46606 Status: Public on May 04 2013 Title: Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4 (expression) Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23684984 Summary & Design: Summary: Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.

Overall design: Resting mature peripheral primary B cells were enriched from the spleens of Irf4+/+ or Irf4-inducible mice on the Irf4-/- background. We sought to compare gene expression profiles of wild type and Irf4 mutant B cells in response to mitogens that promote the differentiation of the B cells into plasma cells and cells that have undergone class switch recombination. Day 0 samples represent RNA analysis of unstimulated cells, whereas Day 1 and Day 3 samples represent analysis of stimulated cells in culture. For stimulation, cells were cultured with insect cell purified CD40L and IL-2/4/5 cytokines for the indicated days. In the case of doxycycline-mediated rescue of IRF4 expression, doxycycline was added at predefined low and high concentrations that yield low or high numbers of plasma cells, respectively (see Molecular Systems Biology 7:495). Each replicate represents analysis of B cells from an individual mouse. Of the three replicates in each group, two were performed in parallel and one was performed at a different time. All cells were lysed using Trizol and total RNA was purified according to manufacturer's suggestions. The high quality of the RNA was confirmed using Agilent Bioanalyzer 2100 system. 250ng of RNA was then processed into biotinylated cRNA according to standard procedures and used to hybridize to Affymetrix 430 2.0 arrays. Signal intensities were normalized using the D-Chip algorithm (PM-only model) and the output was used to quantify differential gene expression between groups.

Background corr dist: KL-Divergence = 0.0934, L1-Distance = 0.0402, L2-Distance = 0.0024, Normal std = 0.4712

0.897 Kernel fit Pairwise Correlations Normal fit

Density 0.448

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

4KO-hiD14KO-hiD3 rep1 4KO-loD1(0.0386298) rep1 4KO-loD3(0.0242642) rep1 4KO-zeroD0(0.0325057) rep1 4KO-zeroD1(0.0155207) rep14KO-zeroD3 (0.0669857) rep14KO-hiD1 (0.022207) rep14KO-hiD3 rep2(0.0181489) 4KO-loD1(0.0293286) rep2 4KO-loD3(0.0208006) rep2 4KO-zeroD0(0.0200444) rep2 4KO-zeroD1(0.0109032) rep24KO-zeroD3 (0.0685059) rep24KO-hiD1 (0.0259448) rep24KO-hiD3 rep3(0.0269056) 4KO-loD1(0.0300631) rep3 4KO-loD3(0.0194722) rep3 4KO-zeroD0(0.0312902) rep3 4KO-zeroD1(0.0107468) rep34KO-zeroD3 (0.0607164) rep3WT-D0 (0.0244853) rep3 rep1WT-D1 (0.0230013) (0.0536709) rep1WT-D3 (0.0404187) rep1WT-D0 (0.027553) rep2WT-D1 (0.0596653) rep2WT-D3 (0.0497244) rep2WT-D0 (0.0235043) rep3WT-D1 (0.0637382) rep3WT-D3 (0.042994) rep3 (0.018261) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 1202.0 2020.0 3135.6 P ( S | Z, I ) = 1.00 Mrps10 509.4 1299.6 2117.9 Mean Corr = 0.80765 Mrpl46 720.2 1423.7 1963.0 Mrps34 1328.2 2841.5 3225.9 Mrpl16 1119.7 1961.7 3112.8 Mrps23 726.5 1650.4 2114.4 Mrpl44 337.0 963.5 1263.1 Mrps30 1117.1 1805.0 2068.4 Apex1 1536.6 3791.9 6394.5 Mrps27 238.6 576.2 923.4 Mrpl45 893.6 2003.6 2802.5 Rpl7l1 1346.8 2790.6 4038.0 Mrpl4 1360.0 1900.3 2109.5 Mrpl50 754.0 1250.7 1996.5 Mrpl54 904.5 1662.5 1977.2 Rps27l 2676.9 8042.8 9424.5 Qtrt1 584.3 799.3 1245.0 Mrpl14 511.9 1087.3 1319.0 Rpl27 13709.4 15036.1 15505.1 Mrpl24 3082.6 3921.0 4321.7 Prmt3 1201.8 1539.3 2851.7 Mrpl12 1068.9 2804.1 5217.8 Stoml2 658.8 1711.4 2508.0 Timm13 2137.5 4092.2 5349.3 Clpp 675.5 1145.3 1936.5 Mrps7 901.8 2364.3 2969.7 CEM 1 + Mrpl11 1179.8 2015.4 3294.5 Top 10 Genes Exosc4 308.0 820.5 1597.2 C1qbp 2818.4 5940.6 9561.4 Phb2 3278.2 5427.5 7515.7 Naa10 1094.3 1836.0 2828.5

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE20954" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 14 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

0.551 Kernel fit Pairwise Correlations Normal fit

Density 0.275

0.000 CEM 1

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

Pre-normalization Quantiles

Mouse lung-embryoMouse lung-embryoMouse day lung-embryoMouse 12-rep1 day lung-embryoMouse 12-rep2 (0.11523) day lung-embryoMouse 14-rep1 (0.134537) day lung-embryoMouse 14-rep2 (0.0674791) day lung-embryoMouse 16-rep1 (0.0950068) day lung-embryoMouse 16-rep2 (0.0717919) day lung-postnatalMouse 18-rep1 (0.0436072) day lung-postnatalMouse 18-rep2 (0.0457696) lung-postnatalMouseday (0.0471779) 2-rep1 lung-postnatalMouseday (0.0440281)2-rep2 lung-postnatalMouseday (0.0436806)10-rep1 lung-postnatalday 10-rep2 (0.0506917) day 30-rep1 (0.0497429) day 30-rep2 (0.0866091)[ min (0.104648) ] [ medium ] [ max ] CEM 1 Mrpl2 913.2 1051.5 1895.6 P ( S | Z, I ) = 1.00 Mrps10 593.7 887.0 1548.7 Mean Corr = 0.79140 Mrpl46 581.9 696.8 1067.5 Mrps34 1002.2 1247.9 1724.5 Mrpl16 783.9 1158.7 2126.7 Mrps23 466.9 739.0 1159.3 Mrpl44 320.3 428.7 675.9 Mrps30 663.8 936.4 1648.0 Apex1 504.0 1010.6 5123.2 Mrps27 203.7 323.5 785.2 Mrpl45 607.3 1104.5 1729.3 Rpl7l1 847.9 1204.3 2593.6 Mrpl4 1432.2 1737.0 2413.5 Mrpl50 480.2 756.2 1838.8 Mrpl54 447.4 819.5 1647.1 Rps27l 3573.5 4810.4 7117.8 Qtrt1 353.1 485.0 1112.4 Mrpl14 1136.1 1493.1 2034.4 Rpl27 12072.0 15805.5 17195.8 Mrpl24 2204.9 2886.6 3895.4 Prmt3 557.7 862.4 2511.5 Mrpl12 948.4 1179.5 3759.2 Stoml2 735.1 1092.2 2644.6 Timm13 1935.1 2721.6 3979.7 Clpp 913.2 1320.5 3080.2 Mrps7 833.0 1027.4 2203.7 CEM 1 + Mrpl11 1153.2 1506.4 3993.7 Top 10 Genes Exosc4 429.1 560.3 1028.7 C1qbp 1112.9 1403.9 4761.9 Phb2 1286.6 1983.2 4670.7 Naa10 651.7 921.0 2940.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE27092" 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=GSE27092 Status: Public on Mar 13 2011 Title: Expression data from P14 TCR cytotoxic T cells overexpressing HDAC7 phosphorylation deficient mutant Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21399638 Summary & Design: Summary: The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile.

Overall design: In vitro generated P14 TCR cytotoxic T cells were retrovirally infected with a construct encoding GFP-HDAC7 phosphorylation deficient mutant, sorted in base of GFP expression (GFP positive and GFP negative) and processed for microarray analysis in three biological replicas.

Background corr dist: KL-Divergence = 0.0166, L1-Distance = 0.0217, L2-Distance = 0.0007, Normal std = 0.7816

0.510 Kernel fit Pairwise Correlations Normal fit

Density 0.255

0.000 CEM 1

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

Pre-normalization Quantiles

GFP negativeGFP negative 1GFP (biological negative 2GFP (biological replicapositive 3GFP (biological 1)replicapositive 1 (0.150708) GFP(biological 2)replicapositive 2 (0.139722) (biological replica3) 3 (0.162788) (biological 1)replica (0.202002) 2)replica (0.153117)[ min 3) (0.191664) ] [ medium ] [ max ] CEM 1 Mrpl2 3381.9 4739.0 5005.1 P ( S | Z, I ) = 1.00 Mrps10 1453.5 2938.7 3336.8 Mean Corr = 0.79043 Mrpl46 2850.9 3885.5 4227.4 Mrps34 5144.0 6270.0 6693.0 Mrpl16 2026.1 3350.5 3525.1 Mrps23 1783.9 2417.4 2623.4 Mrpl44 784.9 947.3 1016.6 Mrps30 1469.6 2124.2 2213.6 Apex1 1870.8 3464.1 3758.1 Mrps27 445.0 688.9 789.7 Mrpl45 1444.1 1793.1 2120.9 Rpl7l1 1536.2 2262.5 2492.5 Mrpl4 3714.0 4227.9 4635.6 Mrpl50 746.2 1064.9 1149.3 Mrpl54 1829.0 2372.9 2720.9 Rps27l 9265.7 14995.3 17051.8 Qtrt1 931.4 1717.9 1855.3 Mrpl14 1151.4 1251.4 1408.8 Rpl27 36155.7 47700.9 49182.6 Mrpl24 3598.1 4000.4 4227.6 Prmt3 1136.2 2020.8 2098.2 Mrpl12 4911.2 8619.5 9450.4 Stoml2 2576.4 3682.3 3933.4 Timm13 6431.4 10741.1 11328.6 Clpp 1753.2 2809.9 2935.8 Mrps7 1970.5 2851.7 3133.1 CEM 1 + Mrpl11 1920.1 2907.4 3297.4 Top 10 Genes Exosc4 1366.3 1479.9 1507.0 C1qbp 5822.3 12874.0 13712.0 Phb2 5667.8 9380.5 10267.0 Naa10 3066.2 4455.9 4841.4

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE38031" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 8 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.456 Kernel fit Pairwise Correlations Normal fit

Density 0.228

0.000 CEM 1

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

Pre-normalization Quantiles

ctrl_rep1ctrl_rep2 (0.130543)ctrl_rep3 (0.0588222)ctrl_rep4 (0.156168)irr_rep1 (0.136839)irr_rep2 (0.147677)irr_rep3 (0.120593)irr_rep4 (0.119395) (0.129962) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 2828.0 4808.6 5415.0 P ( S | Z, I ) = 1.00 Mrps10 1809.7 3055.0 3350.0 Mean Corr = 0.78827 Mrpl46 986.9 1341.3 1496.6 Mrps34 3149.8 5305.1 5783.2 Mrpl16 1598.9 2083.9 2331.4 Mrps23 1502.5 1872.1 2294.2 Mrpl44 630.0 757.0 945.0 Mrps30 1043.3 1928.5 2226.7 Apex1 2890.6 6921.3 7709.1 Mrps27 306.9 674.0 808.1 Mrpl45 1815.6 2988.2 3242.7 Rpl7l1 1366.5 2646.0 2728.6 Mrpl4 2115.9 3219.9 3401.6 Mrpl50 1137.1 1921.4 2092.0 Mrpl54 643.8 1297.0 1530.4 Rps27l 13325.4 15223.3 16033.7 Qtrt1 355.7 776.5 833.3 Mrpl14 1231.0 1843.2 2089.2 Rpl27 17134.0 18705.2 20020.0 Mrpl24 3301.0 3963.6 4323.6 Prmt3 1091.1 1737.2 1884.3 Mrpl12 2377.3 5251.9 5750.9 Stoml2 1332.1 2468.8 2852.4 Timm13 5304.9 7898.0 8167.6 Clpp 2011.4 2747.3 3176.8 Mrps7 2064.2 3854.3 4090.1 CEM 1 + Mrpl11 1812.7 2864.2 3354.6 Top 10 Genes Exosc4 1150.8 1743.5 1958.5 C1qbp 4332.4 7670.8 8335.3 Phb2 2759.0 5657.4 6105.5 Naa10 821.2 2669.5 2950.3

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE53951" 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=GSE53951 Status: Public on Jan 10 2014 Title: Gene expression after type-I interferon treatment in primary neurons, primary fibroblasts and L929 cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24453359 Summary & Design: Summary: Microarray expression profilling of mouse primary mixed cortical/hippocampal neurons, primary fibroblasts and L929 cells to compare ISGs signature in disctinct cell types

Overall design: Primary mixed cortical/hippocampal neurons, primary fibroblasts (MEFs) and L929 cells were mock-treated or treated with 5U/mL of IFN-beta and RNA was harvested after 24 hours. For neurons and fibroblast, 2 samples were analyzed for each condition.

Background corr dist: KL-Divergence = 0.0405, L1-Distance = 0.0863, L2-Distance = 0.0101, Normal std = 0.7845

0.611 Kernel fit Pairwise Correlations Normal fit

Density 0.305

0.000 CEM 1

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

Pre-normalization Quantiles

neurons_mock_sample1neurons_IFNb_sample1neurons_mock_sample2neurons_IFNb_sample2 (0.119211)MEFs_mock_sample1 (0.0983813)MEFs_IFNb_sample1 (0.105196)MEFs_mock_sample2 (0.110097) MEFs_IFNb_sample2(0.0593403) (0.0616831)L929_mock L929_IFNb(0.0447167) (0.170394) (0.0613859) (0.169594) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 730.0 1472.0 2643.9 P ( S | Z, I ) = 1.00 Mrps10 1230.6 1954.0 2884.6 Mean Corr = 0.78335 Mrpl46 802.3 934.5 1079.0 Mrps34 1395.2 2170.0 2392.9 Mrpl16 1444.8 1801.6 2414.7 Mrps23 1004.6 1273.2 1911.2 Mrpl44 424.6 480.6 699.5 Mrps30 767.2 1272.8 1592.1 Apex1 3325.4 3914.9 4463.3 Mrps27 319.4 427.5 874.4 Mrpl45 846.5 1509.9 2679.6 Rpl7l1 830.9 2060.7 2198.5 Mrpl4 1209.1 1702.6 3775.1 Mrpl50 739.0 1245.9 1627.7 Mrpl54 806.3 1637.3 1956.4 Rps27l 5588.1 17289.2 19704.0 Qtrt1 284.7 562.2 859.9 Mrpl14 570.3 749.2 1327.7 Rpl27 12120.4 21337.3 25894.3 Mrpl24 1261.7 2904.2 4969.2 Prmt3 1550.6 1797.6 2702.7 Mrpl12 2601.2 3368.6 5853.7 Stoml2 1004.6 1795.8 2107.7 Timm13 2876.3 3735.6 5574.3 Clpp 1724.6 2011.5 2193.2 Mrps7 934.8 1826.0 2166.5 CEM 1 + Mrpl11 1459.8 1877.8 2334.7 Top 10 Genes Exosc4 583.9 769.9 962.7 C1qbp 2690.6 7131.3 8336.3 Phb2 2179.6 4848.1 5918.4 Naa10 510.6 965.6 2098.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE56345" 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=GSE56345 Status: Public on Mar 29 2014 Title: Therapeutic potential of spleen tyrosine kinase inhibition for treatment of high-risk precursor B-cell acute lymphoblastic leukemia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24828076 Summary & Design: Summary: This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL.

Intensified and central nervous system (CNS)-directed chemotherapy has significantly improved outcomes for pediatric B-acute lymphoblastic leukemia (B-ALL), but confers significant late-effect morbidities. Moreover, many patients suffer relapses, underscoring the need to develop novel, molecularly targeted B-ALL therapies. Using a mouse model, we showed that leukemic B-cells require pre-B-cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) signaling in vivo. In diagnostic samples from human B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated growth of 69 B-ALL samples, including high-risk (HR) subtypes. Orally administered fostamatinib significantly reduced high disease burden after xenotransplantation of HR B-ALL samples into immune-deficient mice, and decreased leukemia dissemination into spleen, liver, kidneys and the CNS of recipients. Thus, SYK activation sustains growth of multiple HR B-ALL subtypes, suggesting that SYK inhibitors may improve outcomes for HR and relapsed B-ALL.

Overall design: B-cell leukemia samples (3) from a mutant mouse model were compared to sorted or cultured preB or proB cells from normal mice using Affymetrix GeneChip arrays.

Background corr dist: KL-Divergence = 0.0709, L1-Distance = 0.0252, L2-Distance = 0.0009, Normal std = 0.5061

0.791 Kernel fit Pairwise Correlations Normal fit

Density 0.396

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_mouse_preBcells_sorted_1wt_mouse_preBcells_sorted_2wt_mouse_preBcells_sorted_3double_mutant_leukemia_lymph_node_1double_mutant_leukemia_lymph_node_2 (0.127039)double_mutant_leukemia_lymph_node_3 (0.134588)wt_mouse_proBcells_cultured_1 (0.103368)wt_mouse_proBcells_cultured_2wt_mouse_proBcells_cultured_3 (0.123167) (0.177726) (0.06507) (0.0956561) (0.0647613)[ min (0.108624) ] [ medium ] [ max ] CEM 1 Mrpl2 1794.7 5293.9 7546.9 P ( S | Z, I ) = 1.00 Mrps10 880.4 1746.5 2105.4 Mean Corr = 0.77858 Mrpl46 1589.5 1884.2 2156.3 Mrps34 1311.8 2511.0 4686.3 Mrpl16 3726.6 4956.3 6309.3 Mrps23 792.5 1466.1 2320.4 Mrpl44 525.5 1083.8 1800.6 Mrps30 927.5 1736.5 3159.6 Apex1 1128.6 6102.0 8666.9 Mrps27 556.4 1000.0 1386.5 Mrpl45 1064.1 1738.4 3618.4 Rpl7l1 1308.5 1745.2 3561.7 Mrpl4 1865.4 3170.5 4773.0 Mrpl50 620.2 831.4 1675.6 Mrpl54 1227.2 2567.2 3811.1 Rps27l 7458.3 16314.0 25243.1 Qtrt1 252.9 776.7 1617.8 Mrpl14 1585.2 2059.5 5696.3 Rpl27 28213.9 33275.2 48462.8 Mrpl24 2306.6 4211.2 6872.4 Prmt3 858.3 1884.8 2758.7 Mrpl12 1609.9 5178.5 11115.3 Stoml2 1129.3 3637.9 5306.5 Timm13 3378.0 6987.5 10861.5 Clpp 819.8 1958.4 3028.5 Mrps7 1093.5 1903.0 2794.6 CEM 1 + Mrpl11 1047.8 3080.9 4408.2 Top 10 Genes Exosc4 704.2 1574.3 3138.7 C1qbp 1224.1 4643.0 15361.3 Phb2 4101.7 7306.0 13808.0 Naa10 682.8 2462.4 4224.4

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE30160" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.522 Kernel fit Pairwise Correlations Normal fit

Density 0.261

0.000 CEM 1

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

Pre-normalization Quantiles

wild typewild replicate typewild replicate 1 type (0.355595)knockin replicate 2 (0.111784)knockin replicate 3 (0.0790385)knock replicate 1 (0.191496) in replicate 2 (0.119798) 3 (0.142288)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1858.2 2375.3 2875.2 P ( S | Z, I ) = 1.00 Mrps10 1275.4 2263.8 3107.4 Mean Corr = 0.77772 Mrpl46 1111.4 1531.7 1840.3 Mrps34 2530.8 4690.5 5587.8 Mrpl16 2038.2 2536.7 3237.6 Mrps23 1520.9 2293.8 2500.6 Mrpl44 1161.5 1572.7 1730.0 Mrps30 1636.7 1982.0 2242.8 Apex1 1901.6 4572.6 6302.3 Mrps27 354.0 572.8 694.3 Mrpl45 2380.3 3144.2 3681.9 Rpl7l1 1461.8 1989.0 2258.5 Mrpl4 2219.7 2567.0 2666.1 Mrpl50 1132.8 1803.2 2052.6 Mrpl54 796.7 1294.0 1413.0 Rps27l 10773.7 12661.2 13194.8 Qtrt1 555.4 654.9 875.4 Mrpl14 1509.5 1971.1 2177.4 Rpl27 16632.0 17843.4 18254.8 Mrpl24 4053.5 4158.0 4513.5 Prmt3 861.7 1918.3 2524.9 Mrpl12 2474.1 5156.4 5912.2 Stoml2 1249.2 1747.9 2416.8 Timm13 4617.3 6911.4 8059.9 Clpp 1069.5 1720.1 2221.7 Mrps7 1526.0 1872.2 2456.1 CEM 1 + Mrpl11 2433.3 3468.0 3950.2 Top 10 Genes Exosc4 1023.9 1393.0 1656.7 C1qbp 3445.2 7003.9 8124.8 Phb2 3652.4 5993.9 6610.0 Naa10 953.1 1922.0 2482.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE13693" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 9 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13693 Status: Public on Feb 06 2009 Title: Gene expression profiling of normal mouse myeloid cell populations Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7RÎ±), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.

Overall design: See summary.

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

0.500 Kernel fit Pairwise Correlations Normal fit

Density 0.250

0.000 CEM 1

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

Pre-normalization Quantiles

NORMALNORMAL BM NEUTROPHILS_2NORMAL BM NEUTROPHILS_1NORMAL BM NEUTROPHILS_3NORMAL (0.196847)MYELOBLASTS_CD117POS_GR1+_MAC1-_1NORMAL (0.233708)MYELOBLASTS_CD117POS_GR1+_MAC1-_2NORMAL (0.180866)MYELOBLASTS_CD117POS_GR1+_MAC1-_3NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_2NORMAL MYELOBLASTS_CD117POS_GR1+_MAC1+_1 MYELOBLASTS_CD117POS_GR1+_MAC1+_3 (0.126597) (0.089026)[ min(0.0734831) (0.0407266)] (0.0215765)[ (0.0371696) medium ] [ max ] CEM 1 Mrpl2 81.4 1440.3 2300.7 P ( S | Z, I ) = 1.00 Mrps10 141.7 1946.2 2485.8 Mean Corr = 0.77259 Mrpl46 109.9 1059.9 1451.6 Mrps34 271.3 2381.3 3029.7 Mrpl16 155.7 1888.2 3601.0 Mrps23 72.7 327.3 426.2 Mrpl44 313.1 1427.4 2128.5 Mrps30 267.6 1727.2 2337.4 Apex1 39.4 2873.5 6647.1 Mrps27 38.7 403.4 880.8 Mrpl45 337.0 1110.3 1524.5 Rpl7l1 1436.2 3656.3 4166.4 Mrpl4 1123.5 1872.1 3212.5 Mrpl50 78.6 994.5 1818.1 Mrpl54 216.5 719.0 1176.8 Rps27l 533.4 4090.5 6719.1 Qtrt1 26.6 596.1 1159.3 Mrpl14 374.3 472.5 645.2 Rpl27 4303.0 12451.9 14119.6 Mrpl24 3776.8 4719.5 5211.3 Prmt3 92.6 2211.4 3227.4 Mrpl12 60.8 2135.9 3792.8 Stoml2 189.9 1869.0 2555.5 Timm13 768.4 3733.9 4498.6 Clpp 178.9 1203.6 1656.3 Mrps7 196.7 1200.8 1708.1 CEM 1 + Mrpl11 38.3 1892.7 3066.9 Top 10 Genes Exosc4 116.4 472.6 683.3 C1qbp 71.3 4783.5 8819.7 Phb2 1356.0 4400.9 6450.0 Naa10 291.9 1849.1 2305.3

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE42238" 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=GSE42238 Status: Public on Feb 19 2013 Title: The C-terminus of CBFˆ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23152542 Summary & Design: Summary: The C-terminus of CBFˆ-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFˆ-SMMHC. To test the role of the fusion protein’s C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFˆ-SMMHC (CBFˆ-SMMHC˛C95). Embryos with a single copy of CBFˆ-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBFˆ-SMMHC˛C95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFˆ-SMMHC˛C95.

To identify gene expression changes induced by CBFˆ-SMMHCDC95, we compared the gene expression profile in the blood cells of Cbfb+/+, Cbfb+/˛C95, and Cbfb˛C95/˛C95 embryonic day 12.5 (E12.5) mice.

Overall design: Cbfb+/˛C95 were mated together to generate Cbfb+/+, Cbfb+/˛C95, and Cbfb˛C95/˛C95 embryos. Blood from 8-10 E12.5 embryos of the same genotype was pooled, and RNA was isolated, labeled, and hybridized to Affymetrix Genechip mouse microarray (430 2.0) chips. 3 chips were used for each genotype.

Background corr dist: KL-Divergence = 0.0484, L1-Distance = 0.0351, L2-Distance = 0.0021, Normal std = 0.5825

0.685 Kernel fit Pairwise Correlations Normal fit

Density 0.342

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

Cbfb˛C95/˛C95Cbfb˛C95/˛C95Cbfb˛C95/˛C95 peripheralCbfb+/˛C95 peripheral blood,Cbfb+/˛C95 peripheral replicateblood,peripheralCbfb+/˛C95 replicateblood,peripheral 1 Cbfb+/+ (0.167123)blood, replicate peripheral 2 Cbfb+/+ replicate(0.175093)blood,peripheral 3 Cbfb+/+ replicate(0.148298)blood,peripheral 1 (0.0472645)blood, replicate peripheral 2 replicate(0.0864388)blood, 3 replicate(0.0598922)blood, 1 (0.11665) replicate 2 (0.0936861)[ min 3 (0.105554) ] [ medium ] [ max ] CEM 1 Mrpl2 3073.6 3771.4 4806.6 P ( S | Z, I ) = 1.00 Mrps10 2275.1 2861.9 4174.6 Mean Corr = 0.77164 Mrpl46 1354.0 1531.7 1878.0 Mrps34 1522.1 2644.1 3056.6 Mrpl16 3186.2 3824.6 4293.4 Mrps23 528.3 634.3 820.1 Mrpl44 402.2 451.6 492.3 Mrps30 1955.3 2080.0 2415.6 Apex1 1133.5 1520.2 2072.3 Mrps27 198.3 239.3 273.2 Mrpl45 966.7 1160.1 1346.0 Rpl7l1 1041.9 1132.0 1733.1 Mrpl4 1418.7 1747.6 1976.1 Mrpl50 1199.3 1355.5 1784.3 Mrpl54 2905.6 3508.6 4145.7 Rps27l 16339.1 17970.7 21768.7 Qtrt1 504.2 624.1 749.4 Mrpl14 2432.0 2732.6 2920.9 Rpl27 53978.6 60595.7 64083.7 Mrpl24 4485.2 5641.4 7041.3 Prmt3 722.3 790.9 846.0 Mrpl12 1818.9 2596.5 3689.4 Stoml2 1662.9 1839.0 2882.9 Timm13 4613.8 6543.9 8079.4 Clpp 1443.3 2305.7 2807.5 Mrps7 1806.6 2506.2 3549.7 CEM 1 + Mrpl11 1057.5 1433.2 1658.6 Top 10 Genes Exosc4 1147.9 1625.7 2276.8 C1qbp 1330.2 2358.0 3103.2 Phb2 4155.8 6259.6 7081.3 Naa10 1305.9 2060.1 2719.8

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE10273" 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=GSE10273 Status: Public on Jan 26 2008 Title: Convergent molecular pathways that induce immunoglobulin light-chain recombination Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18280186 Summary & Design: Summary: Productive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa (Îº) or lambda (Î») light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the ˛” 3† and ˛» enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the Îº intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells.

We used microarrys to identify the changes in gene expression under different levels of the cytokine IL-7 and after rescue of genetic defect.

Keywords: growth conditions and rescue

Overall design: IRF4,8 null pre-B cells were cultures in the indicated conditions prior to RNA isolation and hybridization to Affymetrix arrays.

Background corr dist: KL-Divergence = 0.0485, L1-Distance = 0.0228, L2-Distance = 0.0005, Normal std = 0.5808

0.703 Kernel fit Pairwise Correlations Normal fit

Density 0.351

0.000 CEM 1

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

Pre-normalization Quantiles

IRF4,8 null_IL7hi_rep1IRF4,8 null_IL7lo_rep1IRF4,8 null_+IRF4_rep1IRF4,8 (0.133622) null_IL7hi_rep2IRF4,8 (0.152447) null_IL7lo_rep2IRF4,8 (0.0582408) null_+IRF4_rep2IRF4,8 (0.0528275) null_IL7hi_rep3IRF4,8 (0.17644) null_IL7lo_rep3IRF4,8 (0.0675617) null_+IRF4_rep3 (0.0868202) (0.191531) (0.0805094)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1419.8 2449.3 2696.6 P ( S | Z, I ) = 1.00 Mrps10 829.0 1515.4 1737.7 Mean Corr = 0.75739 Mrpl46 770.5 1336.6 1614.4 Mrps34 925.0 1793.3 2083.2 Mrpl16 982.8 1779.8 2005.4 Mrps23 804.3 1279.6 1472.8 Mrpl44 515.5 773.8 943.1 Mrps30 1394.2 1931.7 2165.4 Apex1 1825.4 5417.1 6607.0 Mrps27 318.1 620.3 721.7 Mrpl45 1270.9 1662.3 1963.0 Rpl7l1 1444.9 2452.1 2789.3 Mrpl4 1279.7 1975.9 2177.7 Mrpl50 661.3 1305.4 1597.5 Mrpl54 562.6 1083.1 1900.9 Rps27l 6576.7 9654.5 12120.9 Qtrt1 287.6 799.4 1065.3 Mrpl14 689.8 880.1 1026.7 Rpl27 17394.2 18085.9 18852.7 Mrpl24 2274.7 2748.8 2907.4 Prmt3 1477.5 2168.4 2902.2 Mrpl12 795.7 2473.7 3162.4 Stoml2 696.0 1468.9 1648.8 Timm13 2139.9 3580.0 3909.2 Clpp 443.1 982.7 1292.8 Mrps7 776.6 1223.5 1330.9 CEM 1 + Mrpl11 1269.9 2313.4 2540.9 Top 10 Genes Exosc4 279.6 625.7 737.6 C1qbp 2095.9 7010.5 9272.6 Phb2 2613.6 5379.7 7419.5 Naa10 1331.6 2411.9 2653.7

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE11973" 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=GSE11973 Status: Public on Jul 31 2008 Title: Wild-type cultured neutrophils versus miR-223 null cultured neutrophils Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18668037 Summary & Design: Summary: This array analysis is to study the regulation of target messages expression in in vitro cultured murine neutrophils versus miR-223 null neutrophils. Culture media was SILAC-IMDM for MS analysis.

Overall design: Wild-type cultured neutrophils versus miR-223 null cultured neutrophils

Background corr dist: KL-Divergence = 0.0336, L1-Distance = 0.0241, L2-Distance = 0.0006, Normal std = 0.6585

0.624 Kernel fit Pairwise Correlations Normal fit

Density 0.312

0.000 CEM 1

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

Pre-normalization Quantiles

NeutrophilsNeutrophils culturedNeutrophils cultured fromNeutrophils miR-223 cultured fromNeutrophils miR-223 cultured null fromNeutrophils mouse miR-223 cultured null from bonemouse wild-type cultured null from marrow bonemouse wild-type frommouse marrow - boneRep wild-type bonemouse 1 [marrow -(0.285992) Repmin marrow bonemouse 2 -(0.120211) Rep marrow] - bone Rep3 (0.156223) 1 marrow -(0.211626) Rep[ 2 -(0.118668)medium Rep 3 (0.10728) ] [ max ] CEM 1 Mrpl2 1030.7 1242.1 1430.1 P ( S | Z, I ) = 1.00 Mrps10 841.0 958.7 1226.4 Mean Corr = 0.75220 Mrpl46 994.3 1144.1 1482.1 Mrps34 2280.0 2389.9 3131.2 Mrpl16 1329.4 1545.0 2011.0 Mrps23 1034.5 1307.3 1870.8 Mrpl44 1093.0 1230.4 1441.5 Mrps30 1087.8 1249.8 1482.9 Apex1 1298.6 1634.4 2001.4 Mrps27 214.4 239.3 321.7 Mrpl45 1870.3 2006.9 2105.5 Rpl7l1 2599.6 3008.3 3448.8 Mrpl4 1274.5 1349.6 1724.4 Mrpl50 419.3 527.8 630.6 Mrpl54 618.2 720.1 947.3 Rps27l 5486.7 6724.5 8441.7 Qtrt1 210.4 248.2 312.8 Mrpl14 1103.9 1281.0 1938.5 Rpl27 14933.9 15967.0 16708.4 Mrpl24 3603.8 4061.4 4964.6 Prmt3 947.9 1159.8 1431.8 Mrpl12 891.1 1163.9 1659.8 Stoml2 1248.7 1567.2 1864.4 Timm13 2908.2 3335.7 4032.2 Clpp 983.8 1148.1 1247.1 Mrps7 829.2 922.0 1113.7 CEM 1 + Mrpl11 1032.4 1272.6 1794.4 Top 10 Genes Exosc4 750.4 846.6 960.2 C1qbp 2082.3 2643.5 2872.2 Phb2 2416.5 2549.3 3034.0 Naa10 1035.0 1173.0 1421.1

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE11220" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 44 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11220 Status: Public on Apr 23 2008 Title: Timecourse of developing mouse placenta, with placental and decidual tissues profiled separately Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18340042 Summary & Design: Summary: We used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0).

At each stage, the fetal placenta and maternal decidual tissues were dissected and profiled separately

Keywords: time course

Overall design: Mouse placentas were obtained from timed pregnant female mice at each timepoint, and fetal tissues were used to confirm embryo staging. Fetal placenta and maternal decidual tissues were dissected and pooled separately for each litter prior to RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1391, L1-Distance = 0.0310, L2-Distance = 0.0019, Normal std = 0.3911

1.020 Kernel fit Pairwise Correlations Normal fit

Density 0.510

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

PlacentaPlacenta e8.5, biologicalPlacenta e8.5, biologicalPlacenta e8.5, rep1, biologicalPlacenta technical e8.5, rep2, biologicalPlacenta technical e8.5, rep1,rep1 biologicalPlacenta (0.0372736)technical e9.0, rep2,rep1 biologicalPlacenta (0.0440808)technical e9.0, rep3rep2 biologicalPlacenta (0.0516209)(0.0368483) e9.0, rep1rep2 biologicalPlacenta (0.0304732)(0.0387646) e10.5, rep2 Placenta(0.0257) biological e10.5, rep3 Placenta(0.0323193) biological e10.5, rep1Placenta biological (0.0680199)e12.0, rep2Placenta biological (0.0313425)e12.0, rep3Placenta biological (0.0202344)e12.0, rep1Placenta biological (0.0130833)e13.5, rep2Placenta biological (0.00942313)e13.5, rep3Placenta biological (0.0160184)e15.0, rep1Placenta biological (0.00672289)e15.0, rep2Placenta biological (0.0105749)e15.0, rep1Placenta biological (0.0156226)e17.0, rep2Placenta biological (0.0211153)e17.0, rep3Placenta biological (0.0218449)e17.0, rep1Placenta biological (0.0192444)e19.0, rep2Placenta biological (0.0238037)e19.0, rep3Placenta biological (0.0429614)P0, rep1 biologicalDecidua (0.0169313)P0, rep2 biologicalDecidua rep1e8.5,(0.0127784) (0.019736)biologicalDecidua rep2e8.5, (0.0146865)biologicalDecidua e8.5, rep1, biological Deciduatechnical e8.5, rep2, biological Deciduatechnical e9.0, rep1,rep1 biological Decidua(0.0152117)technical e9.0, rep2,rep1 biological Decidua(0.0152928)technical e10.5, rep1rep2 (0.0149365)Decidua(0.0272996)biological e10.5, rep2rep2 (0.0166889)Decidua(0.0187607)biological e12.0, rep1 Decidua biological (0.0134841)e12.0, rep2 Decidua biological (0.0207964)e15.0, rep1 Decidua biological (0.0175075)e15.0, rep2 Decidua biological (0.0208663)e17.0, rep1 Decidua biological (0.0184569)e17.0, rep2 Decidua biological (0.0197956)e19.0, rep1 Decidua biological (0.0154434)e19.0, rep2 Decidua biological (0.0102103)P0, rep1 biological (0.0166838)P0, rep2 biological rep1(0.0189156) (0.0188383) rep2 (0.019587)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1081.5 2449.3 4774.0 P ( S | Z, I ) = 1.00 Mrps10 502.2 814.4 1993.4 Mean Corr = 0.75049 Mrpl46 450.6 722.8 1440.8 Mrps34 839.5 1544.7 3491.6 Mrpl16 575.8 995.2 2549.1 Mrps23 414.3 613.0 1252.0 Mrpl44 238.9 383.6 773.9 Mrps30 359.9 571.3 1900.7 Apex1 315.4 660.6 2509.8 Mrps27 284.7 411.3 1021.2 Mrpl45 468.8 644.1 1360.6 Rpl7l1 774.1 1201.5 2740.7 Mrpl4 1415.1 2184.9 3345.0 Mrpl50 356.6 639.6 1518.6 Mrpl54 458.8 958.8 2031.6 Rps27l 1747.2 6856.2 9294.8 Qtrt1 281.7 383.9 1158.2 Mrpl14 461.9 942.6 1588.7 Rpl27 4859.8 11900.8 15609.3 Mrpl24 1129.9 2139.5 2813.6 Prmt3 372.7 726.0 2121.6 Mrpl12 587.2 1055.7 4766.0 Stoml2 489.6 1171.1 2119.8 Timm13 1004.5 2753.5 6200.6 Clpp 699.2 1030.0 2316.5 Mrps7 534.7 864.5 2357.3 CEM 1 + Mrpl11 1020.2 1499.1 3022.3 Top 10 Genes Exosc4 285.5 525.2 1797.0 C1qbp 717.7 1720.8 6983.5 Phb2 1097.8 2830.3 7060.6 Naa10 452.2 914.5 2078.7

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE7275" 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=GSE7275 Status: Public on Sep 05 2007 Title: Evaluation of murine mast cells derived exosomal RNA versus their parental cells MC/9. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17486113 Summary & Design: Summary: Exosomes are vesicles of endocytic origin released by many types of cells into the extracellular environment. In an attempt to further examine the exosome-mediated cellular communication, we show that exosomes from a mouse mast cell line (MC/9), exosomes from primary bone marrow derived mast cells, and exosomes from a human mast cell line (HMC-1) contain RNA but not DNA.

Microarray assessments of exosome-derived RNA revealed that these vesicles contain mRNA from approximately 1200 genes, many of which are unique and not present in the cytoplasmic RNA pool in the donor cell.

Keywords: Exosomal RNA versus their parental cells, MC/9

Overall design: Exosomes were prepared from the supernatant of MC/9 cells by differential centrifugations and filtration. RNA was isolated from the exosomes and their parental cells using Trizo. The microarray experiments were performed by SweGene (www.swegene.org/) according to Affymetrix microarray DNA chip analysis. The experiment was performed in quadruple samples. ExoRNA1, ExoRNA2, ExoRNA3, and ExoRNA4 for the exosomes samples and Mast_cells1, Mast_cells2, Mast_cells3, and Mast_cells4 for the MC/9 cells.

Background corr dist: KL-Divergence = 0.0228, L1-Distance = 0.0688, L2-Distance = 0.0086, Normal std = 0.8711

0.458 Kernel fit Pairwise Correlations Normal fit

Density 0.229

0.000 CEM 1

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

Pre-normalization Quantiles

ExosomalExosomal RNA,Exosomal biological RNA,Exosomal biological RNA, rep1Mast biological(0.119781) RNA, rep2 cellsMast biological(0.168819) RNA, rep3 cellsMast biological(0.212571) RNA, rep4 cellsMast biological(0.10398) RNA, rep1 cells biological(0.0713383) RNA, rep2 biological(0.0914268) rep3 (0.133154) rep4[ (0.0989296)min ] [ medium ] [ max ] CEM 1 Mrpl2 119.2 1224.6 1705.2 P ( S | Z, I ) = 1.00 Mrps10 404.4 786.8 1187.0 Mean Corr = 0.74246 Mrpl46 94.1 760.3 1149.8 Mrps34 72.9 1614.9 2081.6 Mrpl16 610.9 1824.4 2760.1 Mrps23 41.2 1309.8 2077.5 Mrpl44 29.7 450.0 762.5 Mrps30 104.1 916.7 1281.9 Apex1 371.3 2432.5 3260.6 Mrps27 33.8 285.6 405.3 Mrpl45 19.2 978.2 1464.8 Rpl7l1 23.8 1234.3 1753.4 Mrpl4 174.1 1190.4 1566.5 Mrpl50 62.3 717.3 861.5 Mrpl54 142.8 686.8 1387.3 Rps27l 550.2 11298.4 14242.1 Qtrt1 40.9 365.7 582.7 Mrpl14 198.7 1273.7 1941.1 Rpl27 3020.2 30354.6 37224.7 Mrpl24 83.2 2452.1 3028.1 Prmt3 573.0 1608.1 1842.8 Mrpl12 26.3 4460.2 5720.3 Stoml2 45.9 2335.7 3632.2 Timm13 31.7 3434.4 3900.7 Clpp 132.0 1031.8 1174.6 Mrps7 238.5 1381.5 1824.4 CEM 1 + Mrpl11 554.4 1111.0 1388.5 Top 10 Genes Exosc4 38.6 300.0 634.9 C1qbp 60.1 3195.7 6459.0 Phb2 384.5 3511.3 5067.1 Naa10 53.4 1842.4 2159.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE46094" 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=GSE46094 Status: Public on May 01 2014 Title: Expression data from PML-RARÎ± transgenic mouse APL(acute promyelocyte leukemia) cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The differentiation of leukemia stem cells (LSCs) is generally regarded as a one-way alterative process to self-renewal. However, how differentiation impacts LSC stemness has largely been unexplored. Here we show that before reaching terminal differentiation (TD), apical LSCs of mouse acute promyelocytic leukemia passed through a partial differentiation (PD) stage, wherein the leukemia cells re-initiated leukemia via de-differentiation albeit at a reduced rate. Notably, while retinoic acid (RA) preferentially drove the transition of LSC to PD, monocytic Irf8 skewed PD cells to terminal maturation over de-differentiation and/or expansion. Remarkably, the combined use of RA and Irf8 induction depleted the total leukemogenic potential, which indicates that discrete stage- or lineage-specific mechanisms elaborate a step-wise LSC differentiation.

We used microarrays to detail the global programme of gene expression indicating the molecular mechanisms unerlying the the process of LSC step-wise differentiation.

Overall design: Retroviral GFP-labled mouse APL cells (bone marrow sample) were repopulated in vivo through transplantation into syngenic recipients. At the proper time points, the GFP positive APL bone marrow cells were collected and sorted for UNSC, UNPD and UNTD samples through FACS. RA-PD and RA-TD cells were sorted from bone marrow tissue treated with ATRA (all trans retinoic acid) for 5 days. The freshly isolated samples were then lysed for RNA extration. Each sample had two biological replicates.

Background corr dist: KL-Divergence = 0.0755, L1-Distance = 0.0335, L2-Distance = 0.0016, Normal std = 0.5022

0.816 Kernel fit Pairwise Correlations Normal fit

Density 0.408

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

APL SCAPL subset, SCAPL subset,biological PDAPL subset,biological rep1PDAPL subset, biological(0.07695) rep2RAPDAPL biological(0.0505532) subset, rep1RAPDAPL (0.208485) subset, rep2biologicalTDAPL subset, (0.153772) biologicalTD rep1APL subset,biological RATD(0.0761522) rep2APL biological subset, rep1RATD(0.0810848) (0.0959815) subset,rep2biological (0.109848) biological rep1 (0.0382968) rep2[ min (0.108877) ] [ medium ] [ max ] CEM 1 Mrpl2 1634.6 2844.8 4449.8 P ( S | Z, I ) = 1.00 Mrps10 1177.3 2129.7 3371.2 Mean Corr = 0.74106 Mrpl46 929.8 1245.1 1962.9 Mrps34 2751.9 4148.0 6576.4 Mrpl16 1042.2 1948.8 2694.4 Mrps23 1188.2 1634.0 2202.2 Mrpl44 824.0 1086.7 1535.5 Mrps30 704.7 1185.5 1763.6 Apex1 1676.6 4054.5 7018.9 Mrps27 172.9 298.6 527.1 Mrpl45 1560.2 2423.8 3396.2 Rpl7l1 1695.7 2095.7 3164.8 Mrpl4 1639.3 2291.0 3625.4 Mrpl50 666.5 929.2 1130.3 Mrpl54 1050.9 1411.1 3134.7 Rps27l 12680.2 17490.9 27940.3 Qtrt1 316.4 563.3 842.7 Mrpl14 1408.7 2061.5 4109.5 Rpl27 24593.0 31741.5 40646.9 Mrpl24 4136.9 5537.0 8078.8 Prmt3 1179.6 1939.6 2448.0 Mrpl12 1652.7 3784.1 8286.4 Stoml2 1149.4 1701.4 3176.4 Timm13 4428.1 5824.1 10776.8 Clpp 899.5 1782.2 3170.4 Mrps7 946.0 1490.3 2498.2 CEM 1 + Mrpl11 1746.3 2905.0 5238.6 Top 10 Genes Exosc4 1075.9 1415.1 2484.2 C1qbp 2929.7 5650.9 9885.6 Phb2 2828.9 3942.3 7056.0 Naa10 1321.8 2206.4 3703.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE11222" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 42 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE11222 Status: Public on Apr 23 2008 Title: Placental and decidual timecourse samples normalized and modeled with an undissected e17 sample Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 18340042 Summary & Design: Summary: We used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0). For these samples, at each stage the fetal placenta and maternal decidual tissues were dissected and profiled separately (See series 1).

For this experiment (Series 2), placental and decidual timecourse samples were normalized and modeled with two undissected (including placental and decidual tissue) e17 placentas to allow for scaling of values for comparison to the undissected placenta samples used in the publicly available mouse GeneAtlas dataset

Keywords: time course

Overall design: Mouse placentas were obtained from timed pregnant female mice at each timepoint, and fetal tissues were used to confirm embryo staging. For all dissected samples, fetal placenta and maternal decidual tissues were dissected and pooled separately for each litter prior to RNA extraction and hybridization on Affymetrix microarrays.

Background corr dist: KL-Divergence = 0.1507, L1-Distance = 0.0356, L2-Distance = 0.0027, Normal std = 0.3773

1.057 Kernel fit Pairwise Correlations Normal fit

Density 0.529

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

PlacentaPlacenta e8.5, biologicalPlacenta e9.0, biologicalPlacenta e9.0, rep3 biologicalPlacenta(Series e9.0, rep1 biologicalPlacenta(Series2) e10.5, rep2(0.0737287) Placenta(Series 2)biological e10.5, rep3(0.0435912) Placenta(Series 2)biological e10.5, (0.0432126) rep1 Placenta 2) biological (Seriese12.0, (0.0448221) rep2Placenta biological (Series2)e12.0, rep3(0.0861585)Placenta biological (Series2)e12.0, rep1(0.0490899)Placenta biological (Series2)e13.5, rep2(0.0315237)Placenta biological (Series2)e13.5, rep3(0.018158)Placenta biological (Series2)e15.0, rep1(0.0127621)Placenta biological (Series2)e15.0, rep2(0.0231936)Placenta biological (Series2)e15.0, rep1(0.00645593)Placenta biological (Series2)e17.0, rep2(0.00857687)Placenta biological (Series2)e17.0, rep3(0.0149801)Placenta biological (Series2)e17.0, rep1(0.020054)Placenta biological (Series2)e19.0, rep2(0.0219605)Placenta biological (Series2)e19.0, rep3(0.020897)Placenta biological (Series2)P0, rep1(0.024314) biologicalDecidua (Series2)P0, rep2(0.0406787) biologicalDecidua rep1e8.5,(Series2) (0.0146338) (SeriesbiologicalDecidua rep2e8.5,2) (0.0106751) (Series2)biologicalDecidua (0.0198187)e8.5, rep1, 2)biological Deciduatechnical (0.0131263)e8.5, rep2, biological Deciduatechnical e9.0, rep1,rep1 biological Decidua(Seriestechnical e9.0, rep2,rep1 biological Decidua(Seriestechnical2) e10.5, rep1rep2(0.0171434) (SeriesDecidua(Series2)biological e10.5, rep2rep2(0.0148337) (Series2)Decidua(Series2)biological e12.0, (0.0144175) (0.026099)rep1 2)Decidua 2)biological (Seriese12.0, (0.0162717) (0.0191207)rep2 Decidua biological (Series2)e15.0, rep1(0.0125878) Decidua biological (Series2)e15.0, rep2(0.019243) Decidua biological (Series2)e17.0, rep1(0.0158896) Decidua biological (Series2)e17.0, rep2(0.0187848) Decidua biological (Series2)e19.0, rep1(0.0165462) Decidua biological (Series2)e19.0, rep2(0.0161067) Decidua biological (Series2)P0, rep1(0.0136085) biologicalPlacenta (Series2)P0, rep2(0.0100499) biologicalPlacenta rep1(Series2) and (0.0159496) (SeriesDecidua rep22) and (0.0148657) (Series2)Decidua e17.0, (0.0173317) 2) biological e17.0, (0.0173271) biological[ repmin 1 (Series rep ] 2 (Series2) (0.0239063) 2) (0.0375056)[ medium ] [ max ] CEM 1 Mrpl2 1085.7 2326.3 4787.2 P ( S | Z, I ) = 1.00 Mrps10 419.1 752.0 1999.2 Mean Corr = 0.73571 Mrpl46 452.4 666.5 1435.8 Mrps34 841.3 1488.0 3501.0 Mrpl16 455.2 896.7 2102.7 Mrps23 415.2 598.9 1255.1 Mrpl44 240.3 368.8 775.7 Mrps30 361.4 550.3 1905.3 Apex1 317.3 559.3 2441.0 Mrps27 286.4 402.1 1022.9 Mrpl45 470.2 632.9 1365.3 Rpl7l1 776.4 1072.4 2170.4 Mrpl4 1418.4 2041.5 3353.1 Mrpl50 357.6 558.2 1369.0 Mrpl54 459.8 936.5 2037.4 Rps27l 1751.0 6585.0 9309.5 Qtrt1 282.9 377.1 1014.7 Mrpl14 464.4 897.8 1591.6 Rpl27 4876.2 11608.7 15642.8 Mrpl24 1133.4 2037.1 2819.6 Prmt3 373.9 620.5 2130.0 Mrpl12 589.2 1030.0 4779.8 Stoml2 491.6 1004.7 1846.7 Timm13 1006.7 2439.8 6213.9 Clpp 701.9 972.3 2322.7 Mrps7 536.7 790.1 2363.9 CEM 1 + Mrpl11 1023.5 1464.3 3026.8 Top 10 Genes Exosc4 286.7 469.8 1802.2 C1qbp 720.2 1366.1 6891.2 Phb2 1102.8 2723.4 7045.7 Naa10 454.3 859.6 2084.5

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE20391" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -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=GSE20391 Status: Public on Jun 16 2010 Title: Comprehensive expression profiling across primary fetal liver terminal erythroid differentiation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20231426 Summary & Design: Summary: Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).

Overall design: Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic developmentbecause Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis while the single knockouts do not. These serine-threonine kinases phosphorylate, and consequently modify the functions of, several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferationexplained in part by impaired cell cycle progression as well as increased apoptosisand terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesissuch as alpha-globin and mitoferrin 1demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

Background corr dist: KL-Divergence = 0.0629, L1-Distance = 0.0458, L2-Distance = 0.0040, Normal std = 0.5380

0.745 Kernel fit Pairwise Correlations Normal fit

Density 0.373

0.000 CEM 1

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

Pre-normalization Quantiles

sorted-R1sorted-R2 cells,sorted-R3 repl cells, 1 sorted-R5(0.0731937) repl cells, 1 sorted-R1(0.170746) repl cells, 1 sorted-R2(0.0706873) repl cells, 1 sorted-R3(0.0576173) repl cells, 2 sorted-R4(0.0634291) repl cells, 2 sorted-R5(0.0760319) repl cells, 2 sorted-R2(0.0988655) repl cells, 1 sorted-R3(0.041348) repl cells, 2 (0.195) repl cells, 3 (0.113779) repl 3 (0.0393015)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 781.6 2385.0 4425.2 P ( S | Z, I ) = 1.00 Mrps10 207.1 1056.1 3494.4 Mean Corr = 0.73309 Mrpl46 625.4 1732.3 2860.2 Mrps34 579.3 3144.1 6233.6 Mrpl16 1126.5 3638.4 5537.0 Mrps23 242.7 1025.2 2529.7 Mrpl44 98.5 561.3 1822.2 Mrps30 487.8 929.4 2384.1 Apex1 711.4 4251.6 7914.3 Mrps27 22.2 386.1 1166.0 Mrpl45 356.7 1669.2 2838.1 Rpl7l1 750.4 1582.6 3956.0 Mrpl4 859.2 1897.4 2908.4 Mrpl50 255.7 1299.9 2531.5 Mrpl54 370.6 1084.7 1544.9 Rps27l 2223.0 11944.3 15612.6 Qtrt1 69.5 413.8 1374.4 Mrpl14 620.5 1337.1 2639.8 Rpl27 21505.5 32970.1 45963.1 Mrpl24 873.1 3158.9 7477.7 Prmt3 326.0 905.9 3048.4 Mrpl12 549.4 3536.1 11718.9 Stoml2 858.2 2485.7 4159.3 Timm13 1697.5 4434.8 8389.7 Clpp 677.1 1792.9 4010.1 Mrps7 494.5 1737.6 2869.8 CEM 1 + Mrpl11 452.0 2065.0 4450.3 Top 10 Genes Exosc4 118.4 652.0 2003.8 C1qbp 885.6 5354.0 15528.6 Phb2 1773.3 6953.4 13485.5 Naa10 384.9 1495.0 4800.3

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE21944" 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=GSE21944 Status: Public on Jul 02 2010 Title: The orphan nuclear hormone receptor ERRÎ² controls rod photoreceptor survival. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 20534447 Summary & Design: Summary: Mutation of rod photoreceptor-enriched transcription factors is a major cause of inherited blindness. We identified the orphan nuclear hormone receptor ERRÎ² as selectively expressed in rod photoreceptors. Overexpression of ERRÎ² induces expression of rod-specific genes in retinas of both wildtype and in Nrl-/- mice, which lack rod photoreceptors. Mutation of ERRÎ² results in dysfunction and degeneration of rods, while inverse agonists of ERRÎ² trigger rapid rod degeneration, which is rescued by constitutively active mutants of ERRÎ². ERRÎ² coordinates expression of multiple genes that are rate-limiting regulators of ATP generation and consumption in photoreceptors. Furthermore, enhancing ERRÎ² activity rescues photoreceptor defects that result from loss of the photoreceptor-specific transcription factor Crx. Our findings demonstrate that ERRÎ² is a critical regulator of rod photoreceptor function and survival, and suggest that ERRÎ² agonists may be useful in the treatment of certain retinal dystrophies.

Overall design: Affymetrix MOE430 microarrays were used to analyze the expression patterns of P21 mouse retinal tissues. The results were compared across the variable of Genotype, specifically ERRÎ² knockout versus wildtype.

Background corr dist: KL-Divergence = 0.0113, L1-Distance = 0.0143, L2-Distance = 0.0002, Normal std = 0.8473

0.475 Kernel fit Pairwise Correlations Normal fit

Density 0.238

0.000 CEM 1

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

Pre-normalization Quantiles

C57Bl/6C57Bl/6 P21, wildtypeC57Bl/6 P21, wildtype retina,C57Bl/6 x Sv129 1retina,C57Bl/6 x(0.0803452) P21, Sv129 ERRÎ²2C57Bl/6 x(0.0871037) P21, Sv129 -/-ERRÎ² P21, knockoutP21, wildtype -/-ERRÎ² knockout retina, -/- retina, knockout 1retina, (0.162871) 3[ (0.269076) min 2retina, (0.167511) 3 ](0.233093) [ medium ] [ max ] CEM 1 Mrpl2 896.8 1350.3 1539.8 P ( S | Z, I ) = 1.00 Mrps10 488.3 1273.2 1565.2 Mean Corr = 0.73159 Mrpl46 582.9 918.6 1211.1 Mrps34 624.5 1751.9 2312.8 Mrpl16 735.3 938.1 1110.9 Mrps23 221.5 670.3 857.4 Mrpl44 249.4 602.9 709.4 Mrps30 610.6 767.4 852.7 Apex1 443.0 889.4 1224.4 Mrps27 245.3 338.1 433.3 Mrpl45 489.1 1347.3 1453.3 Rpl7l1 495.6 990.8 1497.1 Mrpl4 660.2 1234.0 1358.6 Mrpl50 707.0 951.1 1046.9 Mrpl54 346.2 843.4 1054.7 Rps27l 399.3 879.4 1324.3 Qtrt1 160.5 239.9 287.3 Mrpl14 574.7 950.8 1224.3 Rpl27 3928.1 10050.5 11660.1 Mrpl24 1306.2 2325.7 2726.6 Prmt3 426.6 715.2 787.7 Mrpl12 313.8 1110.5 1467.3 Stoml2 700.5 900.0 1106.7 Timm13 854.8 2534.4 3290.6 Clpp 724.1 1528.6 1807.8 Mrps7 377.5 1010.2 1277.6 CEM 1 + Mrpl11 990.8 1280.0 1712.2 Top 10 Genes Exosc4 336.7 735.1 856.4 C1qbp 321.5 1352.9 1549.3 Phb2 859.6 2340.7 2460.2 Naa10 46.9 380.3 492.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE18587" 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=GSE18587 Status: Public on Sep 21 2011 Title: Specific modulation of mucosal immune response, tolerance and proliferation in mice colonized with A. muciniphila Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21904534 Summary & Design: Summary: Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.

Keywords: Analysis of target gene regulation by using microarrays

Overall design: Adult germ-free female NMRI-KI mice (45 65 days) were used for bacterial mono-association. Two bacterial strains were used in this study, A. muciniphila MucT (ATTC BAA-835) and L. plantarum WCFS1 (NCIMB 8826). A. muciniphila was grown anaerobically in a basal mucin based medium and L. plantarum was grown anaerobically at 37´C in Man-Rogosa-Sharpe broth (MRS; Le Pont de Claix, France). After 7 days of colonization, mice were killed by cervical dislocation and terminal ileum, cecum and ascending colon specimens were sampled.

Background corr dist: KL-Divergence = 0.0560, L1-Distance = 0.0627, L2-Distance = 0.0089, Normal std = 0.5753

0.855 Kernel fit Pairwise Correlations Normal fit

Density 0.427

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

ileum_germ_free_non_inoculated_(pool)ileum_germ_free_inoculated_A.muciniphila_(pool)ileum_germ_free_inoculated_L.plantarum_(pool)caecum_germ_free_non_inoculated_(pool)caecum_germ_free_inoculated_A.muciniphila_(pool)caecum_germ_free_inoculated_L.plantarum_(pool) (0.108488)colon_germ_free_non_inoculated_(pool)colon_germ_free_inoculated_A.muciniphila_(pool) (0.0972651)colon_germ_free_inoculated_L.plantarum_(pool) (0.136445) (0.178129) (0.203487) (0.0633696) (0.0844995)[ min ] (0.0423908) (0.0859248)[ medium ] [ max ] CEM 1 Mrpl2 2550.5 2773.3 4221.9 P ( S | Z, I ) = 1.00 Mrps10 1878.3 2111.0 3249.2 Mean Corr = 0.72450 Mrpl46 1503.2 1909.3 2869.8 Mrps34 2763.1 3601.5 5188.9 Mrpl16 2827.2 3090.5 3766.9 Mrps23 1319.9 2500.0 3862.1 Mrpl44 662.1 967.3 1310.8 Mrps30 879.9 1042.8 1427.7 Apex1 1834.1 2047.3 3081.0 Mrps27 233.6 350.6 485.4 Mrpl45 899.2 1047.6 1223.9 Rpl7l1 1213.6 1412.5 1707.6 Mrpl4 2354.2 2602.1 3286.1 Mrpl50 1446.3 2000.7 2751.6 Mrpl54 1230.3 1332.3 2370.3 Rps27l 15044.1 19591.3 28555.6 Qtrt1 450.1 538.4 632.0 Mrpl14 1960.5 2566.0 3519.7 Rpl27 12272.9 13682.6 17776.2 Mrpl24 6484.0 8088.8 9571.0 Prmt3 563.3 634.2 790.6 Mrpl12 3677.8 5003.9 8955.6 Stoml2 1690.1 1808.5 2703.3 Timm13 4855.2 5594.7 8793.9 Clpp 828.6 1152.1 1478.3 Mrps7 1269.4 1413.0 1824.1 CEM 1 + Mrpl11 1614.0 1943.3 2494.6 Top 10 Genes Exosc4 560.7 714.4 925.9 C1qbp 3353.9 3536.1 4630.4 Phb2 5938.9 6956.0 8000.3 Naa10 1318.9 1533.3 1933.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE6196" 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=GSE6196 Status: Public on Mar 21 2009 Title: Mouse Reissner's Membrane Gene Expression studies Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19144862 Summary & Design: Summary: The goal was to screen for the expressed genes in Reissner's membrane (RM) that are related to ion transport and its regulation. The objectives were 1) to determine whether short-term incubation altered the transcriptome and 2 ) to discover which genes changed expression levels in response to glucocorticoids.

Keywords: drug response

Overall design: RM was dissected free-hand from mouse cochleae and either immediately subjected to RNA extraction or incubated for 24 as explants. Two series of samples were incubated in the presence or absence of dexamethasone (100 nM) and samples of RM were pooled to obtain sufficient material for gene array analysis. The pooled samples were used to hybridize 3 gene array chips for each biological sample.

Background corr dist: KL-Divergence = 0.0363, L1-Distance = 0.0602, L2-Distance = 0.0046, Normal std = 0.7133

0.627 Kernel fit Pairwise Correlations Normal fit

Density 0.313

0.000 CEM 1

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

Pre-normalization Quantiles

KSUAP-DMKSUAP-DM mReissnersKSUAP-DM mReissnersKSUAP-DM Membrane mReissnersKSUAP-DM Membrane mReissners Dex24hrAKSUAP-DM Membrane mReissners Dex24hrBKSUAP-DM (0.0727896) Membrane mReissners Dex24hrCKSUAP-DM (0.100812) Membrane mReissners I24hrAKSUAP-DM (0.0868523) Membrane mReissners (0.0912365)I24hrB Membrane mReissners (0.0892091)I24hrC Membrane (0.0817232)F0hrA Membrane (0.146792) F0hrB[ min (0.160296) F0hrC ](0.17029) [ medium ] [ max ] CEM 1 Mrpl2 1406.2 2408.2 2766.1 P ( S | Z, I ) = 1.00 Mrps10 752.8 2020.3 2353.6 Mean Corr = 0.71550 Mrpl46 804.0 991.5 1117.5 Mrps34 1484.6 1819.1 2115.6 Mrpl16 798.3 1337.1 1440.9 Mrps23 129.4 226.1 298.2 Mrpl44 422.7 485.8 506.0 Mrps30 618.5 1084.4 1267.0 Apex1 510.2 1352.0 1444.1 Mrps27 211.0 315.0 355.2 Mrpl45 474.1 668.3 836.8 Rpl7l1 510.1 993.5 1316.3 Mrpl4 1510.4 2435.9 2554.3 Mrpl50 202.7 312.7 406.4 Mrpl54 283.2 458.7 541.5 Rps27l 2640.5 6964.6 7506.6 Qtrt1 194.3 399.1 453.5 Mrpl14 516.9 585.4 806.3 Rpl27 8500.2 15606.5 17061.1 Mrpl24 3116.4 3440.3 4162.1 Prmt3 884.4 1401.1 1548.3 Mrpl12 824.1 1419.3 1525.6 Stoml2 642.1 1112.9 1427.3 Timm13 2374.3 4173.9 4841.1 Clpp 1468.1 2032.6 2237.4 Mrps7 1001.8 1530.1 1653.8 CEM 1 + Mrpl11 1616.0 1772.5 2245.0 Top 10 Genes Exosc4 316.8 535.4 644.4 C1qbp 1722.5 4628.6 5297.5 Phb2 2016.3 3458.4 4093.6 Naa10 270.1 323.4 433.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE13692" 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=GSE13692 Status: Public on Feb 06 2009 Title: Expression profiling of MLL-AF10 myeloid leukemia cellular subsets Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19200802 Summary & Design: Summary: Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.

Overall design: Leukemic splenocytes from four mice with MLL-AF10 AML were sub-fractionated in to c-kit high and c-kit negative sub-populations by FACS.

Background corr dist: KL-Divergence = 0.0464, L1-Distance = 0.0346, L2-Distance = 0.0017, Normal std = 0.6099

0.681 Kernel fit Pairwise Correlations Normal fit

Density 0.341

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

MLL-AF10MLL-AF10 LEUKEMICMLL-AF10 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_948 LEUKEMIC MLL-AF10SPLENOCYTES_CD117POS_948 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_951 LEUKEMIC MLL-AF10SPLENOCYTES_CD117POS_951 LEUKEMIC MLL-AF10SPLENOCYTES_CD117NEG_952 LEUKEMIC(0.0867501) SPLENOCYTES_CD117POS_952 LEUKEMIC(0.187973) SPLENOCYTES_CD117NEG_953 (0.132669) SPLENOCYTES_CD117POS_953 (0.181448)[ min(0.0867779) (0.0593338) ] (0.101443) [(0.163606) medium ] [ max ] CEM 1 Mrpl2 1430.1 2574.8 3680.1 P ( S | Z, I ) = 1.00 Mrps10 857.0 1668.2 2311.7 Mean Corr = 0.71507 Mrpl46 472.7 586.7 904.7 Mrps34 1168.8 1529.9 2036.7 Mrpl16 1027.5 1271.4 2012.0 Mrps23 162.0 259.4 471.5 Mrpl44 315.7 709.4 949.7 Mrps30 1193.3 1495.7 1741.3 Apex1 1610.6 3397.9 4563.7 Mrps27 232.3 287.6 707.8 Mrpl45 703.5 1329.9 1603.8 Rpl7l1 2819.8 3297.4 4716.0 Mrpl4 1257.4 1445.2 1835.4 Mrpl50 167.8 556.6 639.5 Mrpl54 75.7 179.3 350.3 Rps27l 4079.9 6177.2 6649.0 Qtrt1 167.7 380.9 630.3 Mrpl14 135.3 216.2 324.9 Rpl27 7214.1 11141.8 14312.9 Mrpl24 2414.9 3657.9 4031.1 Prmt3 1799.7 2917.2 3558.8 Mrpl12 1307.1 1741.4 2842.6 Stoml2 854.0 1089.4 1731.5 Timm13 1919.7 3135.5 3891.1 Clpp 336.1 663.1 1332.3 Mrps7 311.2 394.2 720.6 CEM 1 + Mrpl11 1107.7 1250.6 3821.4 Top 10 Genes Exosc4 163.8 335.7 672.7 C1qbp 1424.5 3168.0 5039.1 Phb2 1482.9 1807.5 2840.3 Naa10 707.0 1243.2 1773.4

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 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 (0.0920357)Lin+_KRN_sorted (0.235378)Lin+_KRNxG7_sorted (0.156262)(0.161906) (0.151302) (0.203116)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1405.7 2390.5 2870.9 P ( S | Z, I ) = 1.00 Mrps10 528.7 1181.8 1447.9 Mean Corr = 0.71232 Mrpl46 338.3 565.1 656.1 Mrps34 878.4 1276.0 1418.0 Mrpl16 1245.5 2072.0 2429.9 Mrps23 116.0 176.3 239.2 Mrpl44 207.6 331.2 353.3 Mrps30 730.1 1292.7 1383.3 Apex1 1435.1 4964.8 6144.5 Mrps27 77.8 264.7 314.8 Mrpl45 1222.7 1502.1 1548.2 Rpl7l1 1861.5 2597.2 2786.7 Mrpl4 1247.0 1516.2 1561.1 Mrpl50 221.2 365.8 444.5 Mrpl54 137.8 183.6 209.0 Rps27l 1894.0 3521.7 3792.0 Qtrt1 168.3 628.8 775.6 Mrpl14 168.7 227.5 233.0 Rpl27 4899.4 8141.5 8941.3 Mrpl24 3134.4 4084.6 4891.1 Prmt3 1025.4 2657.2 3414.1 Mrpl12 449.4 1266.4 1757.0 Stoml2 582.1 966.5 1230.9 Timm13 718.2 1083.0 1220.9 Clpp 169.9 483.6 636.5 Mrps7 396.3 641.6 722.9 CEM 1 + Mrpl11 1091.6 2208.1 2373.6 Top 10 Genes Exosc4 77.1 163.1 168.3 C1qbp 1581.6 4101.0 5160.3 Phb2 1269.0 2409.2 2726.6 Naa10 107.5 287.6 381.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE38304" 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=GSE38304 Status: Public on Sep 24 2012 Title: Gene Expression Profiles of MYC+ and MYC- mouse Germinal Center B cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23001145 Summary & Design: Summary: Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas.

We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts.

Overall design: GFPMYC+ and GFPMYC- GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools of GFPMYC knock-in mice (12 days after SRBC immunization). 5-20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays.

Background corr dist: KL-Divergence = 0.0656, L1-Distance = 0.0311, L2-Distance = 0.0016, Normal std = 0.5216

0.766 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

GFPMYCGFPMYC negativeGFPMYC negative GC GFPMYCB negativecells, GC GFPMYC BBiological negativecells, GC GFPMYC BBiological positivecells, GCreplicate GFPMYC BBiological positivecells, GC replicate 1 B(0.10544)GFPMYC Biological cells,positive GC replicate 2 B(0.0768732)Biological cells,positive GC replicate 3 B(0.103038)Biological cells, GCreplicate 4 B(0.148018)Biological cells, replicate 4 (0.10648) Biological[ minreplicate 5 (0.106247) replicate ]6 (0.116196) 7 (0.237708)[ medium ] [ max ] CEM 1 Mrpl2 811.9 1483.8 1917.6 P ( S | Z, I ) = 1.00 Mrps10 635.5 1043.8 1625.7 Mean Corr = 0.69759 Mrpl46 478.3 826.2 1062.3 Mrps34 473.9 661.1 1265.9 Mrpl16 1916.4 2900.7 4827.7 Mrps23 1185.5 1566.2 2591.2 Mrpl44 2070.9 3496.8 5452.8 Mrps30 2558.8 3983.4 5629.3 Apex1 782.9 2918.7 5552.2 Mrps27 279.3 558.7 834.0 Mrpl45 178.2 462.1 661.6 Rpl7l1 901.4 1419.6 2291.0 Mrpl4 495.0 962.9 1088.0 Mrpl50 647.0 1355.7 2324.3 Mrpl54 259.1 394.1 730.4 Rps27l 3632.8 7597.4 10972.4 Qtrt1 137.1 408.0 961.3 Mrpl14 323.3 545.3 1193.2 Rpl27 10743.2 13965.6 20611.3 Mrpl24 4339.9 5906.4 8232.9 Prmt3 3198.7 7038.4 9820.6 Mrpl12 820.1 1535.2 4993.2 Stoml2 746.5 1162.2 2429.8 Timm13 1104.2 1778.9 3868.6 Clpp 241.3 515.3 1145.8 Mrps7 1427.4 2295.4 3820.0 CEM 1 + Mrpl11 1890.3 3356.1 6514.9 Top 10 Genes Exosc4 45.9 179.7 388.1 C1qbp 2680.9 8472.2 12106.6 Phb2 4597.0 7675.1 10683.3 Naa10 688.4 1321.6 2837.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE51608" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

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

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

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

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

0.518 Kernel fit Pairwise Correlations Normal fit

Density 0.259

0.000 CEM 1

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

Pre-normalization Quantiles

Ebf2+ rep1Ebf2+ (0.186451) rep2Ebf2+ (0.149482) rep3Ebf2- (0.161866) rep1Ebf2- (0.210073) rep2Ebf2- (0.127785) rep3 (0.164343) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 670.7 2084.9 2934.5 P ( S | Z, I ) = 1.00 Mrps10 636.4 1630.2 2313.1 Mean Corr = 0.69554 Mrpl46 684.1 1548.6 2780.6 Mrps34 253.6 859.0 1406.1 Mrpl16 211.2 2169.5 2394.3 Mrps23 40.9 367.8 602.0 Mrpl44 99.7 478.1 808.1 Mrps30 600.6 1878.2 2592.0 Apex1 941.8 5501.5 5925.4 Mrps27 91.8 389.6 462.1 Mrpl45 104.4 870.3 1198.0 Rpl7l1 371.3 2395.1 2706.8 Mrpl4 1775.5 2081.8 2724.5 Mrpl50 129.1 519.6 664.8 Mrpl54 113.3 317.9 409.3 Rps27l 1224.4 3131.1 6070.2 Qtrt1 343.1 1057.6 1410.5 Mrpl14 214.9 459.3 577.7 Rpl27 2678.2 3291.5 10802.5 Mrpl24 2909.4 4548.4 5897.4 Prmt3 683.5 4003.6 4488.3 Mrpl12 264.5 2009.6 3307.5 Stoml2 1043.3 2266.6 5126.6 Timm13 601.8 1891.4 4989.4 Clpp 461.6 1360.4 1431.1 Mrps7 762.8 1418.7 1935.4 CEM 1 + Mrpl11 523.5 1776.6 2737.6 Top 10 Genes Exosc4 129.3 403.1 751.3 C1qbp 562.1 6524.8 8770.2 Phb2 1890.6 8587.7 11697.9 Naa10 301.7 436.7 1147.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE12518" 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=GSE12518 Status: Public on Apr 15 2009 Title: Differential expression profile between MNV-1 infected and mock-infected RAW 264.7 cells. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19211757 Summary & Design: Summary: Noroviruses have been widely recognized for their importance as causative agents of non-bacterial gastroenteritis. Mouse norovirus is the only representative of the norovirus genus, family Caliciviridae, able to grow in cell culture. The aim of this study is to describe the differences in the expression profiles of MNV-1 and mock-infected macrophages (RAW 264.7 cells), in order to better understand the response of the host cell to norovirus infection.

Overall design: This study compares two type of samples (MNV-infected and mock-infected RAW cells) in biological triplicates respectively. The MNV stock used for infection was obtained in the same cell line, and purified with a sucrose cushion in order to account for expression changes caused by virus infection only.

Background corr dist: KL-Divergence = 0.0217, L1-Distance = 0.0741, L2-Distance = 0.0057, Normal std = 0.9739

0.425 Kernel fit Pairwise Correlations Normal fit

Density 0.213

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

Macrophages_MNVinfected_12h_rep1Macrophages_MNVinfected_12h_rep2Macrophages_MNVinfected_12h_rep3Macrophages_mock-infected_12h_rep1Macrophages_mock-infected_12h_rep2Macrophages_mock-infected_12h_rep3 (0.464331) (0.119996) (0.0803027) (0.122358)[ (0.113487)min (0.0995249) ] [ medium ] [ max ] CEM 1 Mrpl2 1243.0 2205.4 2496.3 P ( S | Z, I ) = 1.00 Mrps10 859.8 2766.3 2819.4 Mean Corr = 0.69451 Mrpl46 680.8 1300.9 1484.0 Mrps34 1462.4 2881.8 4129.8 Mrpl16 1642.2 2608.6 3212.0 Mrps23 674.2 1660.3 1823.8 Mrpl44 626.5 752.1 966.8 Mrps30 1001.5 1467.6 1790.7 Apex1 2701.4 4469.9 7050.0 Mrps27 384.1 575.9 727.4 Mrpl45 1175.2 3182.5 3494.8 Rpl7l1 1300.0 3290.4 3939.2 Mrpl4 1737.6 3117.9 3616.8 Mrpl50 328.1 1120.7 1209.1 Mrpl54 536.2 1073.2 1228.0 Rps27l 6214.6 16348.5 20369.3 Qtrt1 528.4 567.2 674.1 Mrpl14 631.7 1272.5 1365.0 Rpl27 26608.8 39568.7 49674.7 Mrpl24 2376.9 6427.0 6909.1 Prmt3 1091.8 1684.1 2570.0 Mrpl12 1727.7 4373.0 7083.8 Stoml2 936.3 2364.7 2623.6 Timm13 2331.5 4761.0 6591.8 Clpp 895.6 1792.2 1975.9 Mrps7 843.8 1132.5 1902.1 CEM 1 + Mrpl11 870.4 1688.5 2443.2 Top 10 Genes Exosc4 596.3 1386.0 1482.8 C1qbp 3270.2 9813.0 11690.9 Phb2 5797.5 8440.9 12472.3 Naa10 1069.4 1546.0 1897.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE42883" 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=GSE42883 Status: Public on Jan 15 2013 Title: Gene expression data following Neurogenin 1 expression in mouse embryonic stem cells Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: To study the early gene expression events involved in neurogenesis, we expressed the bHLH neural determination factor neurogenin 1 in mouse embryonic stem cells.

We used microarray to examine the program of gene expression at 24, 48, 72 hours of transgene expression.

Overall design: RNAs from uninduced and induced cells were isolated at 24, 48, and 72 hours of differentiation and subjected to microarray analysis.

Background corr dist: KL-Divergence = 0.0734, L1-Distance = 0.0365, L2-Distance = 0.0022, Normal std = 0.5043

0.815 Kernel fit Pairwise Correlations Normal fit

Density 0.407

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

ESC expressingESC expressingESC Neurog1 expressingESC Neurog1 at expressing 24h,ESC Neurog1 biologicalat expressing 24h,ESC Neurog1 biologicalat expressing 24h,rep1ESC Neurog1 biologicalat(0.26833) expressing 48h,rep2ESC Neurog1 biologicalat(0.0252753) expressing 48h,rep3ESC Neurog1 biologicalat(0.0299369) expressing 48h,repESC Neurog1 1 biologicalat (0.073937)in 72h,rep maintenanceESC Neurog1 2 biologicalat (0.0331507)in 72h,rep maintenanceESC 3 biologicalat (0.0422359)in 72h,culture,rep maintenance 1 biological (0.0926126) culture, repbiological 2 (0.0855099) culture, repbiological rep3 (0.0575796) 1 biological [(0.10696) repmin 2 (0.0702809) rep ] 3 (0.114191)[ medium ] [ max ] CEM 1 Mrpl2 1268.2 1976.3 6218.5 P ( S | Z, I ) = 1.00 Mrps10 1126.6 2156.5 4014.5 Mean Corr = 0.69400 Mrpl46 880.8 1048.4 1906.3 Mrps34 1248.6 2518.9 6581.2 Mrpl16 1360.5 1898.1 4165.6 Mrps23 1212.5 1582.7 2156.8 Mrpl44 556.4 827.8 1369.1 Mrps30 887.8 1459.2 2916.3 Apex1 4929.2 7745.8 13622.0 Mrps27 364.6 901.7 2983.4 Mrpl45 1265.9 2646.1 4843.0 Rpl7l1 1681.7 2557.8 5431.6 Mrpl4 1045.2 1717.4 5497.5 Mrpl50 657.3 1601.3 2476.0 Mrpl54 545.8 940.8 2252.2 Rps27l 10742.8 18950.5 30999.0 Qtrt1 527.7 837.1 2094.2 Mrpl14 606.6 725.0 1376.2 Rpl27 18998.0 29402.3 44391.2 Mrpl24 2691.9 4197.1 6841.8 Prmt3 1632.1 2273.2 2783.6 Mrpl12 1809.6 3321.4 9267.5 Stoml2 1437.3 2278.9 4989.5 Timm13 2314.0 3565.4 8984.6 Clpp 1015.9 1607.1 5051.2 Mrps7 928.6 1367.7 2733.3 CEM 1 + Mrpl11 2122.4 3012.1 6301.4 Top 10 Genes Exosc4 655.8 980.5 2705.4 C1qbp 4204.8 8551.6 14037.0 Phb2 3832.2 6136.1 14991.7 Naa10 1135.2 1679.8 4405.8

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE56135" 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=GSE56135 Status: Public on Jun 15 2014 Title: Intrinsic differences between oral and skin keratinocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: Summary & Design: Summary: The morphology and the behavior of skin and oral tissue keratinocytes are different. One significant dissimilarity between the two sites is the response to injury. Oral and skin keratinocytes have intrinsic differences in the response to injury and such differences are reflected in gene expression profiles.

We used microarrays to investigate differences in global gene expression patterns between baseline skin and oral epithelium sheets without their underlying connective tissue.

Overall design: Paired skin and oral epithelium was separated from the dermis for RNA extraction and hybridization on Affymetrix microarrays. Skin epidermal tissues were obtained from the tail of mice and oral epidermal tissues were obtained from the hard palate. Enzymatically isolated epithelium was used for analysis.

Background corr dist: KL-Divergence = 0.0201, L1-Distance = 0.0140, L2-Distance = 0.0002, Normal std = 0.7354

0.542 Kernel fit Pairwise Correlations Normal fit

Density 0.271

0.000 CEM 1

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

Pre-normalization Quantiles

m1 mousem2 skinmousem4 epithelium skinmousem5 epithelium skinmouse 1 (0.0847613)p1 epithelium mouseskin 2 (0.086258)p2 epithelium palatalmouse 4 (0.0964833)p4 epitheliumpalatalmouse 5 (0.142282)p5 epitheliumpalatalmouse 1 (0.158664) epitheliumpalatal 2 (0.179541) epithelium 4 (0.11369) 5[ (0.138319) min ] [ medium ] [ max ] CEM 1 Mrpl2 1499.6 1700.9 1882.6 P ( S | Z, I ) = 1.00 Mrps10 1518.4 1759.2 2300.5 Mean Corr = 0.68259 Mrpl46 1103.4 1764.9 1863.6 Mrps34 2558.9 3463.1 3975.2 Mrpl16 1953.4 2153.9 2313.6 Mrps23 978.2 1153.9 1524.4 Mrpl44 567.1 712.0 833.8 Mrps30 952.4 1267.0 1351.5 Apex1 2388.0 2642.8 2899.5 Mrps27 271.2 300.9 366.4 Mrpl45 898.1 1176.8 1255.8 Rpl7l1 1332.2 1813.4 2383.2 Mrpl4 1419.1 1673.8 1825.4 Mrpl50 742.9 833.9 1278.6 Mrpl54 1189.5 1716.7 2130.4 Rps27l 8084.8 9296.4 10527.7 Qtrt1 431.1 624.8 688.1 Mrpl14 930.0 1298.0 1667.7 Rpl27 18701.2 19849.1 20077.2 Mrpl24 3170.0 4350.5 5169.9 Prmt3 1293.2 1515.3 1577.6 Mrpl12 1969.2 2473.7 2623.7 Stoml2 1192.1 1574.4 1706.6 Timm13 3683.5 4314.5 5601.0 Clpp 1015.0 1191.2 1513.3 Mrps7 1240.8 1493.6 1992.6 CEM 1 + Mrpl11 1229.6 1430.8 1828.8 Top 10 Genes Exosc4 467.6 621.8 792.8 C1qbp 2196.9 2951.6 3132.7 Phb2 2402.6 2676.4 2876.3 Naa10 1278.0 1412.1 1703.2

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE44923" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 16 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44923 Status: Public on Mar 06 2013 Title: An Epigenetic Component of Hematopoietic Stem Cell Aging Amenable to Reprogramming Into a Young State Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23476050 Summary & Design: Summary: Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. While it is well established that many of the age-induced changes are intrinsic to HSCs, less is known about the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and following the transplantation of 're-differentiated' HSCs into new hosts; the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results therefore favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging rather than being driven by an increased DNA mutation burden.

Overall design: Hematopoietic stem cells (HSC) have been sorted out from young and aged steady-state mice, and from recipients transplanted with young and aged bone marrow. Generated iPS and commercially available ES cells were also sorted and analyzed.

Background corr dist: KL-Divergence = 0.0286, L1-Distance = 0.0494, L2-Distance = 0.0038, Normal std = 0.7036

0.567 Kernel fit Pairwise Correlations Normal fit

Density 0.284

0.000 CEM 1

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

Pre-normalization Quantiles

Young transplantedYoung transplantedAged HSC,transplantedAged biological HSC,transplantedES cells biologicalHSC, replicateES from biological cells HSC, OpenreplicateAged 1from biological(0.129644) Biosystems replicatesteady-state PrimogenixAged 2 (0.0990578) replicatesteady-state 1Aged (0.0881885) (0.063363) (0.0589668)male steady-state 2Young (0.103132)HSC, male steady-statebiologicalYoung HSC, male steady-statebiologicalYoung HSC, replicate male steady-statebiologicaliPS replicateHSC, cells 1male (0.0393787)iPS biologicalof replicateHSC, cells a 2male aged(0.0314944)iPS biologicalof HSC, cells hematopoieticreplicatea3 aged(0.0374277)iPS biologicalof cellshematopoieticreplicatea 1young (0.0351815) of origin,replicatea hematopoietic2young (0.0343585) biologicalorigin, hematopoietic3 (0.0284092) biological origin, replicate[ min biologicalorigin, replicate 1 (0.0566409) ]biological replicate2 (0.0675592) replicate 1[ (0.0656025) medium 2 (0.0615947) ] [ max ] CEM 1 Mrpl2 514.2 2611.2 5137.2 P ( S | Z, I ) = 1.00 Mrps10 462.2 865.6 2290.7 Mean Corr = 0.68153 Mrpl46 258.3 811.5 2982.4 Mrps34 268.2 888.8 3078.0 Mrpl16 1227.6 2073.7 2988.6 Mrps23 92.3 204.0 293.3 Mrpl44 354.3 894.8 1089.9 Mrps30 889.2 1164.2 4308.7 Apex1 1226.6 4014.8 8475.6 Mrps27 211.1 330.4 1409.6 Mrpl45 198.5 785.5 2928.5 Rpl7l1 347.5 2081.8 4302.5 Mrpl4 699.7 1145.2 3969.0 Mrpl50 234.3 580.0 1111.2 Mrpl54 123.4 279.2 994.8 Rps27l 1176.5 4948.8 10172.3 Qtrt1 587.1 1210.7 3378.7 Mrpl14 118.4 283.0 713.5 Rpl27 6160.9 12511.8 17239.4 Mrpl24 2587.8 4501.3 5523.4 Prmt3 1429.2 2889.0 3628.6 Mrpl12 285.6 1268.6 5008.2 Stoml2 352.1 1545.0 5004.8 Timm13 353.9 1262.0 5932.8 Clpp 220.9 1178.0 3739.8 Mrps7 775.4 996.4 2438.7 CEM 1 + Mrpl11 702.8 1776.7 4545.3 Top 10 Genes Exosc4 200.6 362.2 3283.0 C1qbp 3595.5 8522.8 10879.2 Phb2 2147.4 5133.9 8279.8 Naa10 309.6 676.3 2080.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE5127" 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=GSE5127 Status: Public on Sep 01 2006 Title: Gene Expression Biomarkers for Predicting Lung Tumors in Two-Year Rodent Bioassays Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 17114358 Summary & Design: Summary: Two-year rodent bioassays play a central role in evaluating both the carcinogenic potential of a chemical and generating quantitative information on the dose-response behavior for chemical risk assessments. The bioassays involved are expensive and time-consuming, requiring nearly lifetime exposures (two years) in mice and rats and costing $2 to $4 million per chemical. Since there are approximately 80,000 chemicals registered for commercial use in the United States and 2,000 more are added each year, applying animal bioassays to all chemicals of concern is clearly impossible. To efficiently and economically identify carcinogens prior to widespread use and human exposure, alternatives to the two-year rodent bioassay must be developed. In this study, animals were exposed for 13 weeks to two chemicals that were positive for lung tumors in the two-year rodent bioassay, two chemicals that were negative for tumors, and two vehicle controls. Gene expression analysis was performed on the lungs of the animals to assess the potential for identifying gene expression biomarkers that can predict tumor formation in a two-year bioassay following a 13 week exposure.

Keywords: toxicology, chemical carcinogenesis, lung

Overall design: Five week old female B6C3F1 mice were exposed for 13 weeks to the following treatments: 1) 1,5-Naphthalenediamine, CAS No. 2243-62-1, feed, 2000 ppm, positive lung carcinogen; 2) 2,3-Benzofuran, CAS No. 271-89-6, gavage, 240 mg/kg, positive lung carcinogen; 3) N-(1-naphthyl)ethylenediamine dihydrochloride, CAS No. 1465-25-4, feed, 2000 ppm, negative lung carcinogen; 4) Pentachloronitrobenzene, CAS No. 82-68-8, feed, 8187 ppm, negative lung carcinogen; 5) Feed control; 6) Corn oil gavage control. Feed animals were exposed 7 days/week and gavage animals were exposed 5 days/week (5 ml/kg). Microarray analysis was performed on the lungs of three mice per treatment group.

Background corr dist: KL-Divergence = 0.1443, L1-Distance = 0.0395, L2-Distance = 0.0032, Normal std = 0.3779

1.056 Kernel fit Pairwise Correlations Normal fit

Density 0.528

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

LungTissue_GavageTreatment_CornOil_Control_Animal22LungTissue_GavageTreatment_CornOil_Control_Animal24LungTissue_GavageTreatment_CornOil_Control_Animal25LungTissue_FeedTreatment_RodentLungTissue_FeedTreatment_RodentLungTissue_FeedTreatment_RodentLungTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal12LungTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal14 Chow_Control_Animal27(0.0597496)LungTissue_FeedTreatment_N-(1-naphthyl)ethylenediamineDihydrochloride_Animal15 Chow_Control_Animal28(0.058403)LungTissue_FeedTreatment_1,5-Naphthalenediamine_Animal2 Chow_Control_Animal29(0.0467791)LungTissue_FeedTreatment_1,5-Naphthalenediamine_Animal4LungTissue_FeedTreatment_1,5-Naphthalenediamine_Animal5 (0.0503378)LungTissue_GavageTreatment_2,3-Benzofuran_Animal10 (0.0335725)LungTissue_GavageTreatment_2,3-Benzofuran_Animal6 (0.0438146)LungTissue_GavageTreatment_2,3-Benzofuran_Animal8LungTissue_FeedTreatment_Pentachloronitrobenzene_Animal18LungTissue_FeedTreatment_Pentachloronitrobenzene_Animal16LungTissue_FeedTreatment_Pentachloronitrobenzene_Animal20 (0.024024) (0.0486722) (0.0310477) (0.0246322) (0.024363) (0.0676347) (0.326963) (0.0327151)[ min (0.0216776) ] (0.0426627)[ medium(0.035753) (0.0271982) ] [ max ] CEM 1 Mrpl2 1156.4 1279.3 1745.6 P ( S | Z, I ) = 1.00 Mrps10 662.2 772.9 1279.9 Mean Corr = 0.67829 Mrpl46 704.6 783.5 1334.8 Mrps34 1397.1 1623.4 2313.8 Mrpl16 1075.1 1211.7 1510.7 Mrps23 483.4 633.1 1174.6 Mrpl44 348.5 441.4 795.2 Mrps30 572.6 649.0 859.9 Apex1 714.3 790.3 1183.3 Mrps27 146.3 180.5 293.2 Mrpl45 533.9 573.7 819.4 Rpl7l1 634.0 1034.0 1208.3 Mrpl4 1033.8 1231.8 1789.4 Mrpl50 772.2 907.0 1400.4 Mrpl54 297.2 374.8 861.3 Rps27l 3722.6 4583.2 9511.7 Qtrt1 310.6 405.8 518.4 Mrpl14 1300.8 1706.1 2519.9 Rpl27 13122.8 14905.2 17370.9 Mrpl24 2583.8 2866.9 3597.8 Prmt3 501.4 653.6 877.7 Mrpl12 962.5 1148.5 2042.4 Stoml2 807.4 958.6 1552.6 Timm13 1752.5 2273.8 3849.5 Clpp 1037.9 1345.9 1803.6 Mrps7 704.4 789.8 1276.9 CEM 1 + Mrpl11 945.8 1145.6 1573.1 Top 10 Genes Exosc4 415.4 547.7 781.2 C1qbp 1054.2 1294.1 1902.7 Phb2 1577.3 1754.1 2650.6 Naa10 530.7 651.1 886.4

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE47872" 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=GSE47872 Status: Public on Mar 26 2014 Title: Integrated analysis identifies key determinants of embryonic stem cell identity and homeostasis Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 24711389 Summary & Design: Summary: Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators.

Overall design: Microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Ncl siRNA #1 (Invitrogen, 17975-MSS206961) Ncl siRNA #2 (Invitrogen, 17975-MSS275939), and Control siRNA duplex targeting firefly luciferase.

Background corr dist: KL-Divergence = 0.0151, L1-Distance = 0.0201, L2-Distance = 0.0004, Normal std = 0.8200

0.498 Kernel fit Pairwise Correlations Normal fit

Density 0.249

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 ES cellsNcl-KD ES 96hr, cells Ncl-KDrep1ES 96hr, cells (0.197581) Ncl-KDrep2ES siRNA cells (0.254015) Ncl-KDES #1siRNA cells96hr, ES #1 siRNArep1 cells96hr, (0.165264) #2 siRNArep2 96hr, (0.101097) #2 rep1 96hr, (0.155363)[ rep2min (0.12668) ] [ medium ] [ max ] CEM 1 Mrpl2 4450.6 4835.7 6659.8 P ( S | Z, I ) = 1.00 Mrps10 2310.2 2649.7 3229.4 Mean Corr = 0.66841 Mrpl46 1691.8 1849.2 2195.9 Mrps34 3778.6 4246.1 4380.7 Mrpl16 2491.3 2805.5 3103.1 Mrps23 1089.2 1308.2 1850.4 Mrpl44 882.1 989.7 1385.9 Mrps30 2188.3 2431.3 2523.3 Apex1 7919.9 8410.7 11221.0 Mrps27 896.9 1047.0 1167.2 Mrpl45 4647.5 5343.7 5635.1 Rpl7l1 2998.1 3039.0 3363.4 Mrpl4 2371.1 2591.3 2977.6 Mrpl50 1582.2 1669.1 2740.8 Mrpl54 979.4 1147.1 1719.4 Rps27l 22564.1 24499.5 25065.2 Qtrt1 1236.1 1364.0 1679.3 Mrpl14 595.4 721.0 852.6 Rpl27 24945.8 25946.0 28864.3 Mrpl24 4219.1 5043.3 6249.9 Prmt3 2526.6 2630.4 2742.5 Mrpl12 3468.1 4184.6 5469.6 Stoml2 2402.5 2776.8 3445.1 Timm13 5454.5 5934.0 6300.7 Clpp 3913.6 4613.8 5077.6 Mrps7 1927.8 2249.5 2355.8 CEM 1 + Mrpl11 3117.4 3497.8 4415.0 Top 10 Genes Exosc4 1116.0 1448.1 2225.7 C1qbp 10466.1 10992.7 11339.6 Phb2 6103.8 6265.0 7086.8 Naa10 1637.8 2122.3 2623.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 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,(0.0840679) 1 type (0.120317) sample,mice, replica brainVastusmice, replica wild biological tissue wild2biological muscletypeLateralis,(0.0510722) 2 type (0.0771211) sample,mice, replica brainVastusmice, replica mutant biological tissue mutant3biological muscleLateralis,(0.0696444) 3 mice, (0.0676382) sample, mice,replica brainVastus biological replica mutant biological tissue mutant4 Lateralis,(0.0685548) 4 mice, (0.0717907) replicasample, mice, replica biological mutant 1biological mutant(0.0765637) 1 (0.0680267) mice, replica mice, replica[ biological min 2biological (0.0572737) 2 (0.0542379) replica] replica 3 (0.0820143) 3 (0.051677)[ medium ] [ max ] CEM 1 Mrpl2 1064.6 3772.2 4587.5 P ( S | Z, I ) = 1.00 Mrps10 878.8 2491.8 2973.6 Mean Corr = 0.66777 Mrpl46 859.0 1017.7 1267.5 Mrps34 1648.5 3004.9 3693.8 Mrpl16 1762.3 3693.3 4110.1 Mrps23 552.7 2176.4 2781.1 Mrpl44 395.6 976.7 1264.4 Mrps30 711.4 1271.6 1729.4 Apex1 1481.8 1614.5 1871.6 Mrps27 305.4 403.6 556.9 Mrpl45 927.9 1472.7 1817.4 Rpl7l1 716.2 1201.3 1504.5 Mrpl4 1344.1 2305.1 2696.3 Mrpl50 596.3 1252.0 1837.4 Mrpl54 400.5 1211.7 1617.6 Rps27l 982.7 6581.3 7940.6 Qtrt1 156.0 233.3 289.5 Mrpl14 565.7 1732.2 2495.4 Rpl27 6053.3 10675.5 11307.6 Mrpl24 1852.3 3330.7 3840.6 Prmt3 658.3 1114.9 1220.5 Mrpl12 1537.0 3367.1 4082.2 Stoml2 878.8 2132.5 2530.7 Timm13 2404.8 3799.9 4055.3 Clpp 1000.4 1562.7 1720.5 Mrps7 719.1 1750.1 2135.8 CEM 1 + Mrpl11 1525.4 2725.1 3395.4 Top 10 Genes Exosc4 481.6 721.0 928.6 C1qbp 1922.0 3901.8 4729.2 Phb2 1554.4 4330.0 4852.5 Naa10 328.9 898.9 1186.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE26616" 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=GSE26616 Status: Public on Jun 09 2011 Title: EZH1 and EZH2 Co-Govern Histone H3-K27 Trimethylation and Are Essential for Hair Follicle Homeostasis and Wound Repair Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21317239 Summary & Design: Summary: Polycomb protein group (PcG)-dependent trimethylation on H3-K27(H3K27me3) regulates identity of embryonic stem cells (SCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3-K27-methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly-targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA-microarray studies reveal that despite these striking phenotypic differences, similar genes are upregulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are a) PcG-controlled non-skin lineage genes, whose expression is still significantly lower than in native tissues, and b) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they only partially so in epidermal-progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing towards the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3.

Overall design: RNAs from FACS-purified WT and Ezh1/2 2KO ORS, matrix and epidermal cells (Rendl et al., 2005) were provided to the Genomics Core Facility, MSKCC for quality control, quantification, reverse transcription, labeling and hybridization to MOE430A 2.0 microarray chips (Affymetrix). Arrays were scanned per the manufacturers specifications for the Affymetrix MOE430v2 chip. Images were background-subtracted. Probesets were identified as differentially expressed when the absolute fold change was ¥2. Probesets selected for visualization were log2 transformed and were analyzed with hierarchical clustering (Pearson correlation, average linkage), and visualized with heatmaps to assist in interpretation.

Background corr dist: KL-Divergence = 0.0410, L1-Distance = 0.0331, L2-Distance = 0.0015, Normal std = 0.6238

0.652 Kernel fit Pairwise Correlations Normal fit

Density 0.326

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

Ezh1/2 2KOEzh1/2 FACS 2KOEzh1/2 purified FACS 2KOEzh1/2 purified basalFACS WTEzh1/2 epidermal purifiedFACS matrix WTEzh1/2 purified FACS cellsORS cells WT (0.10734) cellspurified basalFACS(0.112038) (0.208248) epidermal purified matrix cellsORS cells [ (0.360647)cells (0.118747)min (0.0929794) ] [ medium ] [ max ] CEM 1 Mrpl2 1206.1 1893.3 2196.6 P ( S | Z, I ) = 1.00 Mrps10 868.9 1214.8 1959.6 Mean Corr = 0.66580 Mrpl46 585.1 832.5 1243.5 Mrps34 1816.9 3150.8 3740.8 Mrpl16 1058.9 1432.9 2330.0 Mrps23 601.2 1129.5 1941.4 Mrpl44 253.0 507.4 602.1 Mrps30 710.5 1076.0 1472.0 Apex1 3101.5 4587.5 6020.7 Mrps27 314.7 462.3 814.8 Mrpl45 838.4 1485.7 1691.0 Rpl7l1 716.5 1241.5 2251.9 Mrpl4 2112.2 2690.2 3504.6 Mrpl50 694.4 856.1 1374.4 Mrpl54 980.4 1288.5 1774.8 Rps27l 9831.3 14167.2 16806.5 Qtrt1 483.2 532.6 892.3 Mrpl14 646.5 878.2 964.0 Rpl27 22008.9 25279.3 27226.3 Mrpl24 3295.3 4613.1 5566.0 Prmt3 1157.4 1466.8 2088.8 Mrpl12 2271.0 4165.2 5682.9 Stoml2 1383.7 2045.4 2606.9 Timm13 2666.7 3908.4 5233.0 Clpp 915.0 1554.0 2181.5 Mrps7 1063.6 1573.7 2202.6 CEM 1 + Mrpl11 1130.2 1756.6 3193.9 Top 10 Genes Exosc4 361.1 687.0 1198.7 C1qbp 4986.6 5968.0 8850.1 Phb2 4397.2 6163.3 7336.6 Naa10 1447.2 2111.4 3062.1

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE35593" 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=GSE35593 Status: Public on Feb 16 2013 Title: Foxo1/3 depletion in granulosa cells reveals novel mechanisms controlling follicle growth and death and endocrine regulation of pituitary FSH. Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23322722 Summary & Design: Summary: The Foxo transcription factors regulate multiple cellular functions. Foxo1 and Foxo3 are highly expressed in granulosa cells of ovarian follicles. Selective depletion of the Foxo1 and Foxo3 genes in granulosa cells revealed a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb. Equally notable and independent of FSH, depletion of Foxo1/3 altered the expression of specific genes associated with follicle growth versus apoptosis by disrupting critical regulatory interactions of Foxo1/3 with the activin and BMP2 pathways, respectively. As a consequence, granulosa cell proliferation and apoptosis were decreased. These data provide the first evidence that Foxo1/3 divergently regulate follicle growth or death by interacting with the activin and BMP pathways in granulosa cells and by modulating pituitary FSH production.

Overall design: A direct comparison of ovarian granulosa cells from wild type d25, Foxo1/3 dKO d25 and Foxo1/3 dKO 2 month mice.

Background corr dist: KL-Divergence = 0.0309, L1-Distance = 0.0235, L2-Distance = 0.0007, Normal std = 0.6734

0.601 Kernel fit Pairwise Correlations Normal fit

Density 0.301

0.000 CEM 1

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

Pre-normalization Quantiles

S22860_wt_d25_Rep1S22861_wt_d25_Rep2S22864_F_d25_Rep1 S22865_F_d25_Rep2(0.140076) S22862_F_2m_Rep1(0.197246) (0.099207)S22863_F_2m_Rep2 (0.0642755) (0.382012) (0.117183)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 3087.8 3806.6 3827.9 P ( S | Z, I ) = 1.00 Mrps10 1091.0 1377.3 1529.3 Mean Corr = 0.66449 Mrpl46 786.8 997.1 1040.7 Mrps34 1979.6 2376.2 2710.7 Mrpl16 1110.1 1599.9 1673.0 Mrps23 692.0 856.7 957.9 Mrpl44 414.0 587.9 692.8 Mrps30 1356.8 1973.3 2468.1 Apex1 2054.3 3044.4 3620.3 Mrps27 275.0 437.9 489.0 Mrpl45 496.2 682.6 950.2 Rpl7l1 534.5 706.6 941.2 Mrpl4 2095.4 2203.2 2342.6 Mrpl50 710.3 1010.0 1102.5 Mrpl54 808.1 1080.9 1109.4 Rps27l 8224.3 9940.5 10816.4 Qtrt1 795.3 878.9 967.8 Mrpl14 1029.3 1280.5 1490.1 Rpl27 9887.3 12247.1 13002.0 Mrpl24 3060.9 3558.4 3681.9 Prmt3 782.6 1152.1 1549.8 Mrpl12 1950.8 2923.0 3121.2 Stoml2 1301.5 1819.7 2027.0 Timm13 2985.8 3735.5 4314.1 Clpp 1638.3 1883.9 2103.5 Mrps7 1224.9 1601.6 1699.6 CEM 1 + Mrpl11 1318.5 1952.4 2202.2 Top 10 Genes Exosc4 605.4 916.2 1062.9 C1qbp 3165.8 5016.4 5701.6 Phb2 3242.4 4474.5 4671.8 Naa10 795.3 1113.6 1145.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE44175" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 18 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44175 Status: Public on Feb 09 2013 Title: Expression data from mouse embyonic stem cell, neural progenitor and neuron Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23775126 Summary & Design: Summary: The effect of HMGN1 protein on gene expression of mouse ESC, NP and Neurons were investigated by comparing the transcriptome between Hmgn1+/+ and Hmgn1 -/- cells.

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

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

0.471 Kernel fit Pairwise Correlations Normal fit

Density 0.236

0.000 CEM 1

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

Pre-normalization Quantiles

EmbyonicEmbyonic stemEmbyonic cell, stem Hmgn1+/+,Neural cell, stem Hmgn1+/+, progenitor,Neural cell, biological Hmgn1+/+, progenitor,Neural biological Hmgn1+/+, rep1 progenitor,Neuron, biological (0.0646243) Hmgn1+/+, rep2Neuron, biological Hmgn1+/+, (0.0645971) Hmgn1+/+, rep3Neuron, biological Hmgn1+/+, (0.0769193)rep1 biologicalEmbyonic biological(0.0306786)Hmgn1+/+, rep2 biologicalEmbyonic rep1(0.0258636) stem rep3 biological(0.0723647)Embyonic rep2cell,(0.0246998) stem (0.0672465)Hmgn1-/-,Neural rep3cell, stem (0.059845)Hmgn1-/-, progenitor,Neural cell, biological Hmgn1-/-, progenitor,Neural biological Hmgn1-/-,rep1 progenitor,Neuron, biological(0.0663807) Hmgn1-/-,rep2 biologicalNeuron, Hmgn1-/-, (0.0671914) Hmgn1-/-,rep3 biologicalNeuron, Hmgn1-/-, (0.0786374)rep1 biological biological(0.0235246) Hmgn1-/-, rep2 biological rep1(0.0254181) rep3 biological(0.0699295) rep2(0.0220403) (0.0868323) rep3[ min (0.0732069) ] [ medium ] [ max ] CEM 1 Mrpl2 1530.6 2508.4 3731.6 P ( S | Z, I ) = 1.00 Mrps10 1169.0 1705.4 3571.9 Mean Corr = 0.66257 Mrpl46 1014.2 2223.6 2525.2 Mrps34 2421.4 2812.4 3190.2 Mrpl16 1018.4 1773.7 2488.9 Mrps23 518.0 933.9 1191.8 Mrpl44 512.4 891.0 1342.7 Mrps30 875.9 1689.3 2832.9 Apex1 1679.2 5248.3 6970.8 Mrps27 139.8 386.9 766.4 Mrpl45 1697.7 2939.8 5879.1 Rpl7l1 840.5 2196.7 4112.6 Mrpl4 917.0 1929.6 2784.0 Mrpl50 875.5 1423.7 2050.8 Mrpl54 749.0 1198.9 1576.9 Rps27l 6292.4 14847.1 17226.2 Qtrt1 445.5 1052.8 1463.4 Mrpl14 789.5 998.4 1197.4 Rpl27 15246.7 17726.4 19026.0 Mrpl24 2400.9 2881.1 6219.9 Prmt3 701.4 1849.7 3922.4 Mrpl12 1456.0 3284.4 4227.8 Stoml2 1524.3 2959.4 4021.3 Timm13 4112.2 5134.5 6140.2 Clpp 1238.8 2298.6 2470.2 Mrps7 1031.7 1909.6 2558.4 CEM 1 + Mrpl11 1484.1 2647.6 3858.6 Top 10 Genes Exosc4 651.0 1348.9 1627.0 C1qbp 2763.1 7990.8 11718.0 Phb2 1919.6 4913.9 5642.6 Naa10 778.1 1686.0 2022.3

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE31028" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 6 -3.0 -2.0 -1.0 0.0 1.0 2.0 3.0

GEO Link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31028 Status: Public on Sep 02 2011 Title: Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21885018 Summary & Design: Summary: Mouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.

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

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

0.594 Kernel fit Pairwise Correlations Normal fit

Density 0.297

0.000 CEM 1

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

Pre-normalization Quantiles

QuiescentQuiescent hair Activatedfollicle hair Activatedstemfollicle hair cells, follicleTransient-amplifyingstem hair rep1 cells, stemfollicleTransient-amplifying (0.152546) rep2 cells, stem (0.173624) rep1 cells, matrix (0.133576) rep2 cells,matrix (0.0892918) rep1 cells,[ (0.177655)min rep2 (0.273307) ] [ medium ] [ max ] CEM 1 Mrpl2 2044.2 2556.3 3299.2 P ( S | Z, I ) = 1.00 Mrps10 880.0 1206.8 1508.7 Mean Corr = 0.66129 Mrpl46 1118.4 1294.3 1688.0 Mrps34 2777.5 3360.2 3544.7 Mrpl16 1347.2 1669.5 2820.7 Mrps23 885.4 1186.5 1750.7 Mrpl44 775.4 964.6 1212.6 Mrps30 1280.8 1407.1 2015.8 Apex1 2075.3 3667.6 8075.5 Mrps27 211.9 330.8 533.9 Mrpl45 978.2 1116.3 1639.4 Rpl7l1 1390.8 2000.9 2458.9 Mrpl4 1741.7 2152.9 3037.9 Mrpl50 997.2 1162.3 1871.5 Mrpl54 1231.4 1654.0 2021.7 Rps27l 19812.9 20913.2 22445.7 Qtrt1 354.7 420.9 738.9 Mrpl14 1025.5 1166.6 1336.2 Rpl27 32306.1 34830.7 36672.1 Mrpl24 5759.3 6331.1 7281.2 Prmt3 1009.2 1181.8 2297.4 Mrpl12 2547.2 2960.1 5639.4 Stoml2 1730.4 2454.5 3625.2 Timm13 4397.3 6207.6 7970.0 Clpp 1359.4 1816.8 2260.0 Mrps7 1760.1 1827.5 2619.2 CEM 1 + Mrpl11 1097.9 1614.8 3734.8 Top 10 Genes Exosc4 772.7 1136.0 1288.0 C1qbp 3545.3 4434.8 9068.7 Phb2 3412.1 4597.7 7805.8 Naa10 1425.9 1811.8 4322.1

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE17728" 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=GSE17728 Status: Public on May 26 2012 Title: Blood gene expression profile from mouse C57Bl/10 exposed to chronic hypoxia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 22629407 Summary & Design: Summary: In order to study the gene expression profile in C57Bl/10 mouse blood, we exposed three different groups of animals. First was exposed to PO2 21% or normoxia. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. The blood was extracted from inferior vena cava, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.

Overall design: Each group of C57Bl/10 mouse had 4 individuals and they were divided into three different groups of animals. First was exposed to PO2 21% or normoxia for 14 days. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. After the exposure period, the animals were anaesthetized with a mix of Ketamine (100 mg/mL) and xylasine (20 mg/mL) in a proportion of 1:1. A incison was made on abdominal area and from kidneis and liver area of inferior vena cava venus blood was collected The blood was extracted from inferior vena cava. Then, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.

Background corr dist: KL-Divergence = 0.0545, L1-Distance = 0.0470, L2-Distance = 0.0038, Normal std = 0.5640

0.707 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

Blood C57Bl/10Blood C57Bl/10Blood mouse C57Bl/10Blood normoxiamouse C57Bl/10Blood normoxiamouse sample C57Bl/10Blood normoxicmouse sample1 (0.0685559) C57Bl/10Blood normoxicmouse sample2 (0.0432104) C57Bl/10Blood normobaricmouse sample3 (0.0254931) C57Bl/10Blood normobaricmouse 4 hypoxia(0.0256209) C57Bl/10Blood normobaricmouse hypoxia C57Bl/10sampleBlood normobaricmouse hypoxia C57Bl/10 sample1Blood recoverymouse(0.126804) hypoxia C57Bl/10 sample2 recoverymouse(0.0902947) sample sample3 recoverymouse(0.0837116) sample1 (0.0609216) 4 recovery(0.145217) sample2 (0.130673)[ minsample3 (0.127855) 4 ](0.0716432) [ medium ] [ max ] CEM 1 Mrpl2 105.9 722.1 1609.2 P ( S | Z, I ) = 1.00 Mrps10 143.4 474.6 911.3 Mean Corr = 0.66087 Mrpl46 146.2 389.3 1075.1 Mrps34 24.0 543.7 1689.6 Mrpl16 258.6 1075.5 3107.7 Mrps23 142.4 784.6 1638.5 Mrpl44 183.3 1048.5 2271.9 Mrps30 589.9 1340.7 2726.8 Apex1 106.9 573.2 1434.2 Mrps27 23.1 150.1 415.4 Mrpl45 28.2 181.3 451.1 Rpl7l1 221.3 578.4 1550.6 Mrpl4 313.6 555.6 906.5 Mrpl50 11.0 286.3 498.4 Mrpl54 136.7 290.3 620.4 Rps27l 988.0 1997.8 6244.5 Qtrt1 130.3 242.1 383.1 Mrpl14 22.4 293.8 727.1 Rpl27 16285.9 20862.2 82890.7 Mrpl24 1073.2 6017.0 7782.3 Prmt3 301.7 1668.7 2812.8 Mrpl12 215.0 738.2 2601.8 Stoml2 405.9 532.8 956.2 Timm13 245.5 785.9 2604.8 Clpp 34.9 368.5 1057.5 Mrps7 304.9 1199.8 2215.8 CEM 1 + Mrpl11 202.0 1018.8 2939.7 Top 10 Genes Exosc4 28.9 161.3 613.2 C1qbp 197.8 1487.0 3884.5 Phb2 600.8 3246.6 6844.6 Naa10 379.3 668.2 1737.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE25645" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 17 -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=GSE25645 Status: Public on May 09 2011 Title: Ebf1 or Pax5 Haploinsufficiency Synergizes with STAT5 Activation to Initiate Acute Lymphoblastic Leukemia Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21606506 Summary & Design: Summary: STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1 but this had little affect on most EBF1 or PAX5 target genes. However, a subset of these genes was deregulated and included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.

Overall design: Gene expression profiling was performed on cells isolated from lymph nodes of Stat5b-CA x Ebf1+/- and Stat5b-CA x Rag2-/- leukemic mice and pre B cells sorted from bone marrow of C57BL/6 mice and Stat5b-CA transgenic mice. 17 Samples.

Background corr dist: KL-Divergence = 0.0897, L1-Distance = 0.0378, L2-Distance = 0.0030, Normal std = 0.4540

0.879 Kernel fit Pairwise Correlations Normal fit

Density 0.439

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 preBWT #1 preB (0.0465512)WT #2 preB (0.0198992)WT #3 preB (0.0725221)WT #4 preB (0.0375499)Stat5b-CA #5 (0.0367245)Stat5b-CA preBStat5b-CA #1 preB (0.0352686)Stat5b-CA #2 preB (0.045447)Stat5b-CA #3 preB (0.0248683)Stat5b-CA #4 x (0.0680453) Ebf1+/-Stat5b-CA x Ebf1+/-LeukemiaStat5b-CA x Ebf1+/-LeukemaiStat5b-CA #1 x(0.0547156) Ebf1+/-LeukemiaStat5b-CA #2 x(0.129879) Ebf1+/-LeukemiaStat5b-CA #3 x(0.0317191) Rag2-/-LeukemiaStat5b-CA #4 x(0.0545713) Rag2-/-Leukemia #5 x(0.111528) Rag2-/-Leukemia #1 (0.0599473) Leukemia #2 (0.0655772)[ #3 min (0.105186) ] [ medium ] [ max ] CEM 1 Mrpl2 1332.9 1929.2 2803.8 P ( S | Z, I ) = 1.00 Mrps10 764.9 1123.2 1918.8 Mean Corr = 0.65951 Mrpl46 988.0 1528.2 1759.8 Mrps34 1540.7 2106.7 3482.7 Mrpl16 1458.7 1967.5 2871.5 Mrps23 532.4 963.9 1253.9 Mrpl44 536.5 788.8 1226.8 Mrps30 1265.0 1553.7 2013.8 Apex1 1116.9 1974.1 6183.2 Mrps27 491.8 656.1 1273.0 Mrpl45 586.1 1063.9 1414.5 Rpl7l1 636.9 1042.7 1408.4 Mrpl4 965.8 1724.1 2320.6 Mrpl50 484.2 945.8 1444.6 Mrpl54 861.2 1538.7 2571.6 Rps27l 3587.6 6500.1 11870.0 Qtrt1 438.0 534.1 1073.5 Mrpl14 823.0 1349.6 1932.0 Rpl27 14012.6 16431.9 18686.1 Mrpl24 2097.9 3005.5 3666.5 Prmt3 1036.4 1384.3 3192.5 Mrpl12 1189.8 2015.4 4148.9 Stoml2 824.2 1490.4 2460.0 Timm13 2122.9 4013.1 5279.3 Clpp 773.3 1095.6 1606.0 Mrps7 905.6 1339.4 1621.5 CEM 1 + Mrpl11 1758.6 2898.7 4895.1 Top 10 Genes Exosc4 324.7 726.0 1059.4 C1qbp 1647.2 2755.6 6959.1 Phb2 1769.7 3477.8 4936.7 Naa10 633.2 1319.9 2578.5

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE17709" 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=GSE17709 Status: Public on Aug 19 2009 Title: Gene expression analysis of a podocyte specific PTIP deletion in mouse glomerular preparations at 1 month of age Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21060806 Summary & Design: Summary: Glomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.

These mice develop protein urea by 3 months of age. This study was designed to find gene expression differences prior to the onset of the phenotype.

Overall design: Kidneys were excised at 1 month of age. Glomeruli enriched fractions were generated by sieving of the tissue homogenates. RNA was prepared from glomerular enriched fractions.

Background corr dist: KL-Divergence = 0.0391, L1-Distance = 0.0385, L2-Distance = 0.0021, Normal std = 0.6195

0.644 Kernel fit Pairwise Correlations Normal fit

Density 0.322

0.000 CEM 1

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

Pre-normalization Quantiles

wild-type,wild-type, PTIP+,wild-type, rep1PTIP+, wild-type,(0.0208214) rep2PTIP+, wild-type,(0.0252307) rep3PTIP+, wild-type,(0.027274) rep4PTIP+, wild-type,(0.106322) rep5PTIP+, wild-type,(0.0527839) rep6PTIP+, Pod-Cre,(0.0402471) rep7PTIP+, Pod-Cre,(0.0610468) PTIP-,rep8 Pod-Cre,(0.0618084) rep1 PTIP-, (0.0297608)Pod-Cre, rep2 PTIP-, (0.0271044)Pod-Cre, rep3 PTIP-, (0.0191552)Pod-Cre, rep4 PTIP-, (0.016183)Pod-Cre, rep5 PTIP-, (0.0897679)Pod-Cre, rep6 PTIP-, (0.20789)Pod-Cre, rep7 PTIP-, (0.0253889)Pod-Cre, rep8 PTIP-, (0.0392648) rep9 PTIP-, (0.0860625) rep10 (0.0638884)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 691.4 1315.8 2960.4 P ( S | Z, I ) = 1.00 Mrps10 580.3 1256.7 1713.0 Mean Corr = 0.65778 Mrpl46 555.7 956.6 1477.3 Mrps34 280.3 842.0 2446.6 Mrpl16 1599.3 2730.5 3645.2 Mrps23 32.7 495.5 1187.1 Mrpl44 766.0 1390.0 2766.5 Mrps30 1485.9 1879.6 2287.4 Apex1 234.2 527.5 800.7 Mrps27 306.3 608.9 752.1 Mrpl45 63.1 375.7 655.4 Rpl7l1 563.0 1047.6 1305.6 Mrpl4 590.8 1544.1 1961.4 Mrpl50 391.4 1816.9 2744.4 Mrpl54 112.7 491.4 622.6 Rps27l 5026.0 6195.0 7482.1 Qtrt1 96.1 182.6 289.6 Mrpl14 91.3 471.2 1075.0 Rpl27 2272.4 2870.9 5450.9 Mrpl24 3096.4 3899.6 5725.2 Prmt3 1020.9 1480.9 2289.3 Mrpl12 2796.6 4747.1 6796.9 Stoml2 328.4 716.2 1342.3 Timm13 509.4 2034.2 4298.5 Clpp 255.6 956.2 1906.5 Mrps7 1552.6 2231.5 3644.1 CEM 1 + Mrpl11 681.7 1784.0 2294.9 Top 10 Genes Exosc4 123.3 409.3 807.1 C1qbp 2247.3 3439.2 4703.8 Phb2 1971.0 3386.1 6268.2 Naa10 107.6 512.2 972.0

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE32311" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -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=GSE32311 Status: Public on Nov 13 2011 Title: Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis Organism: Mus musculus Experiment type: Genome binding/occupancy profiling by high throughput sequencing Platform: GPL1261 Pubmed ID: 22080921 Summary & Design: Summary: Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2u Nucleosome Remodeling and Deacetylase (NuRD) complex is controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethers this complex to active lymphoid differentiation genes, but keeps it in a functionally-poised state. Loss in Ikaros DNA binding activity causes a local increase in Mi-2u chromatin remodeling, histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributes to transcriptionally-poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their re-activation. Thus release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally-opposing epigenetic mechanisms and genetic networks.

We used microarrays to detail the global programme of gene expression of mouse DP thymocyte after Ikaros inactivation with dominant negative of Ik at different stage.

Overall design: 8 samples (mouse DP thymocytes from wt, and different stage after Ikaros inactivation) are analyzed Mouse Microarray Expression platforms, Affymetrix Mouse 430 2.0. Examination of different histone modifications and binding sites for Ikaros, Mi2beta in wild type DP thymocytes, and Ikaros knockout thymocytes.

Background corr dist: KL-Divergence = 0.0614, L1-Distance = 0.0258, L2-Distance = 0.0011, Normal std = 0.5185

0.769 Kernel fit Pairwise Correlations Normal fit

Density 0.385

0.000 CEM 1

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

Pre-normalization Quantiles

DP wt thymocyte,DP wt thymocyte,DP biologicalwt thymocyte,Ikaros biological rep1KOIkaros thymocyte biological(0.0783372) rep2KOIkaros thymocyte (0.0815042) rep3stageKOIkaros thymocyte (0.0481836) 1, stagedominant Ikarosbiological 1, stagedominant Ikarosbiological negative rep1 1, dominant Ikaros biological(0.0822257) negative rep2thymocyte dominantIkaros (0.0695464) negative rep3thymocyte dominantstage (0.0632334) negative thymocyte 2 stage(16 negative thymocyted), 2 biological stage(16 thymocyted), 2 biological stage[(27 rep1min d), 2 biologicalstage(0.17832)(27 rep2 d),] 3, biological(0.188578) biological rep1 (0.0525326) rep2[ rep1 medium (0.0652357) (0.0923026) ] [ max ] CEM 1 Mrpl2 996.4 1447.1 2627.4 P ( S | Z, I ) = 1.00 Mrps10 689.1 961.7 1963.1 Mean Corr = 0.65723 Mrpl46 1000.5 1292.8 2125.1 Mrps34 1966.7 2861.2 3983.9 Mrpl16 932.6 1240.8 2373.9 Mrps23 639.9 824.9 1519.5 Mrpl44 496.3 533.1 796.5 Mrps30 1294.5 1568.1 2551.7 Apex1 544.4 1373.8 4631.9 Mrps27 343.2 431.0 626.3 Mrpl45 1224.8 1881.2 2893.6 Rpl7l1 996.2 1157.4 1684.9 Mrpl4 1007.2 1651.3 2499.3 Mrpl50 596.9 830.3 1700.3 Mrpl54 869.9 1241.4 2110.5 Rps27l 7979.7 10597.0 18328.3 Qtrt1 284.0 376.8 966.8 Mrpl14 523.5 779.6 1375.2 Rpl27 21972.1 26488.9 29703.7 Mrpl24 4142.2 5125.5 6390.2 Prmt3 812.3 1611.0 3185.0 Mrpl12 1348.8 2678.1 3799.1 Stoml2 714.1 1282.9 2406.7 Timm13 2934.6 4291.1 5234.1 Clpp 741.2 1128.2 1757.1 Mrps7 753.7 1120.7 1766.4 CEM 1 + Mrpl11 1358.2 1561.5 2765.0 Top 10 Genes Exosc4 550.6 740.0 979.7 C1qbp 1257.4 3606.5 8655.3 Phb2 2612.7 4217.1 6631.3 Naa10 1072.6 1785.6 3301.7

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE13547" 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=GSE13547 Status: Public on Apr 17 2009 Title: Zfx controls BCR-induced proliferation and survival of B lymphocytes Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 19329779 Summary & Design: Summary: The development, homeostasis and function of B lymphocytes involve multiple rounds of B cell receptor (BCR)-controlled proliferation and prolonged maintenance. We analyzed the role of transcription factor Zfx, a recently identified regulator of stem cell maintenance, in B cell development and homeostasis. Conditional Zfx deletion in the bone marrow blocked B cell development at the pre-BCR selection checkpoint. Zfx deficiency in peripheral B cells caused impaired generation of the B-1 cell lineage, accelerated B cell turnover, depletion of mature recirculating cells, and delayed T-dependent antibody responses. Zfx-deficient B cells showed normal proximal BCR signaling, but impaired BCR-induced proliferation and survival. This was accompanied by aberrantly enhanced and prolonged integrated stress response, and delayed induction of Cyclin D2 and Bcl-xL proteins. Thus, Zfx restrains the stress response and couples antigen receptor signaling to B cell expansion and maintenance during development and peripheral homeostasis.

Keywords: Expression profiling by array

Overall design: For global gene expression analysis, 2.5 x 105 flow-sorted follicular B cells (B220+ AA4.1- CD23hi CD21int) were cultured in 200 Î¼L B cell media containing 10 Î¼g/mL Î±-IgM for 0, 2, and 12 hrs. Cells were harvested in Trizol (Invitrogen). Total RNA was isolated using Trizol (Invitrogen), and 100 ng of each RNA sample were used for reverse transcription and two rounds of linear antisense RNA amplification/labeling (Ambion). The aRNA was amplified without labeling in the first round, and then labeled with Biotin-16-UTP(Roche Applied Sciences) and Biotin-11-CTP (PerkinElmer Life Sciences) in the second round. Labeled aRNA was fragmented in RNA Fragmentation Buffer (QIAGEN) prior to hybridization. Labeled RNA samples (10 ug/array) were hybridized in duplicate to Mouse Genome 430 2.0 arrays (Affymetrix) at the Columbia University Microarray Project core facility according to the manufacturer's instructions. Quality control and normalization were performed using positive and negative hybridization controls (Affymetrix) spiked into the RNA prior to labeling. Linear amplification of RNA was confirmed for every sample. Array scanning and raw data processing were done using GCOS 1.4 software (Affymetrix).

Background corr dist: KL-Divergence = 0.0888, L1-Distance = 0.0336, L2-Distance = 0.0016, Normal std = 0.4757

0.859 Kernel fit Pairwise Correlations Normal fit

Density 0.429

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

ZFXwt_BZFXwt_B cell_0hr_rep1ZFXwt_B cell_0hr_rep2ZFXwt_B (0.0936669) cell_2hr_rep1ZFXwt_B (0.0902235) cell_2hr_rep2ZFXwt_B (0.0540325) cell_12hr_rep1ZFXcko_B (0.0462979) cell_12hr_rep2ZFXcko_B (0.076589) cell_0hr_rep1ZFXcko_B (0.0795606) cell_0hr_rep2ZFXcko_B (0.0785963) cell_2hr_rep1ZFXcko_B (0.0793319) cell_2hr_rep2ZFXcko_B (0.0824178) cell_12hr_rep1 (0.0865002) cell_12hr_rep2 (0.119386) (0.113397)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 2127.3 3966.9 10385.7 P ( S | Z, I ) = 1.00 Mrps10 1164.1 3634.6 4912.7 Mean Corr = 0.65105 Mrpl46 1922.2 3703.9 4707.1 Mrps34 1146.8 1747.1 2931.0 Mrpl16 2158.4 5474.1 6882.0 Mrps23 22.6 410.2 879.1 Mrpl44 339.4 762.8 1539.7 Mrps30 1173.2 1887.2 2258.2 Apex1 1219.1 5000.6 8820.8 Mrps27 448.7 646.8 1117.1 Mrpl45 650.4 1449.6 2628.4 Rpl7l1 1465.0 4421.3 5897.2 Mrpl4 1554.1 2291.4 4780.3 Mrpl50 216.0 1927.2 2807.0 Mrpl54 427.9 847.7 1099.3 Rps27l 1220.8 10465.1 13150.3 Qtrt1 693.1 3255.4 5906.6 Mrpl14 206.4 324.1 786.6 Rpl27 24053.6 41253.2 48236.6 Mrpl24 1837.0 2846.5 6036.0 Prmt3 2085.8 3927.7 5159.2 Mrpl12 1210.5 4454.6 6209.8 Stoml2 2045.0 3846.5 6410.0 Timm13 3917.7 5137.2 9061.6 Clpp 857.0 2289.5 3310.2 Mrps7 1451.8 2816.3 4338.2 CEM 1 + Mrpl11 796.7 1812.2 4372.9 Top 10 Genes Exosc4 717.4 1056.5 2725.6 C1qbp 1988.6 10911.1 13675.5 Phb2 947.1 4269.1 7423.6 Naa10 308.6 441.2 1450.1

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 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 (0.129176) induction, rep2 biologicalMEFdox1Div_rep1 (0.163814) (0.0632738) biologicalMEFdox1Div_rep2 rep1 (0.0265521) (0.121434)MEFdox2Div_rep1 rep2 (0.0663617) (0.256873)MEFdox2Div_rep2 (0.0474488) (0.0680208) (0.0570464)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 1500.7 1913.9 2495.9 P ( S | Z, I ) = 1.00 Mrps10 2130.6 2722.6 3264.0 Mean Corr = 0.64786 Mrpl46 760.9 878.9 1246.7 Mrps34 2505.7 3127.2 3880.5 Mrpl16 1301.3 1892.3 3064.3 Mrps23 868.0 1151.3 1603.4 Mrpl44 321.1 429.2 845.9 Mrps30 1063.8 1473.7 2676.7 Apex1 1876.2 3385.4 4511.4 Mrps27 228.0 372.8 704.0 Mrpl45 846.8 1445.5 2312.7 Rpl7l1 1170.9 1483.7 1902.2 Mrpl4 1326.5 1725.4 2579.0 Mrpl50 581.7 955.2 1438.0 Mrpl54 749.2 854.0 924.6 Rps27l 15018.4 18132.3 19728.6 Qtrt1 616.5 917.0 1499.3 Mrpl14 1017.7 1181.1 1309.6 Rpl27 14119.3 17100.8 17940.0 Mrpl24 3306.9 3862.0 4863.6 Prmt3 922.9 1602.1 1996.0 Mrpl12 1642.8 2438.0 4994.4 Stoml2 1138.1 1548.0 2446.9 Timm13 4127.7 5419.5 8357.0 Clpp 1272.8 1612.5 1985.0 Mrps7 1622.0 1812.2 2314.9 CEM 1 + Mrpl11 1175.7 1399.2 1573.9 Top 10 Genes Exosc4 725.9 1009.0 1537.2 C1qbp 2753.7 6124.0 10682.5 Phb2 2629.3 4796.7 7800.8 Naa10 668.0 1442.8 2920.6

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE7759" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 112 -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=GSE7759

Background corr dist: KL-Divergence = 0.3284, L1-Distance = 0.0565, L2-Distance = 0.0079, Normal std = 0.2710 GEO Series "GSE40685" Expression Profiles Scale of expression profile Z-scores Num of samples in this series: 11 -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=GSE40685 Status: Public on Sep 28 2012 Title: Foxp3 exploits a preexistent enhancer landscape for regulatory T cell lineage specification [Expression] Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 23021222 Summary & Design: Summary: Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis. It is unclear whether Foxp3 exerts its Treg lineage specification function through active modification of the chromatin landscape and establishment of new enhancers or by exploiting a pre-existing enhancer landscape. Analysis of the chromatin accessibility of Foxp3-bound enhancers in Treg and Foxp3-negative T cells showed that Foxp3 was bound overwhelmingly to pre-accessible enhancers occupied by its cofactors in precursor cells or a structurally related predecessor. Furthermore, the bulk of Foxp3-bound Treg cell enhancers inaccessible in Foxp3- CD4+ cells became accessible upon T cell receptor activation prior to Foxp3 expression with only a small subset associated with several functionally important genes being exclusively Treg cell-specific. Thus, in a late cellular differentiation process Foxp3 defines Treg cell functionality in an opportunistic manner by largely exploiting the preformed enhancer network instead of establishing a new enhancer landscape.

Overall design: Array expression. Three cell types with 3-5 replicates each.

Background corr dist: KL-Divergence = 0.0865, L1-Distance = 0.0219, L2-Distance = 0.0007, Normal std = 0.4629

0.862 Kernel fit Pairwise Correlations Normal fit

Density 0.431

0.000 CEM 1

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

Pre-normalization Quantiles

TN_rep1TN_rep2 (0.0915301)TN_rep3 (0.0793671)Treg_rep1 (0.0594046)Treg_rep2 (0.0417801)Treg_rep3 (0.0573657)Treg_rep4 (0.0514994)Treg_rep5 (0.0744653)GFPKO_rep1 (0.116016)GFPKO_rep2 (0.26054)GFPKO_rep3 (0.0841827) (0.0838492) [ min ] [ medium ] [ max ] CEM 1 Mrpl2 1578.0 2948.3 3812.5 P ( S | Z, I ) = 1.00 Mrps10 618.9 1027.8 1344.0 Mean Corr = 0.64595 Mrpl46 1432.9 2115.0 2403.5 Mrps34 3937.7 6381.0 7919.6 Mrpl16 1427.0 2055.8 2686.0 Mrps23 1138.1 1782.6 2366.3 Mrpl44 809.7 1206.6 1393.1 Mrps30 1476.3 2135.5 2320.7 Apex1 1704.4 2697.2 3126.8 Mrps27 213.5 499.5 584.8 Mrpl45 1343.3 1805.7 2355.1 Rpl7l1 941.8 1566.5 1870.5 Mrpl4 1811.4 3304.7 4200.8 Mrpl50 688.1 944.3 1164.3 Mrpl54 814.2 1541.6 2022.7 Rps27l 5244.8 7189.6 10802.5 Qtrt1 677.3 1061.6 1413.6 Mrpl14 753.4 1400.9 2011.0 Rpl27 49986.3 54015.3 57695.3 Mrpl24 6871.4 8987.4 9600.9 Prmt3 1593.8 1896.4 2246.1 Mrpl12 2114.8 4064.8 5526.6 Stoml2 1591.8 1988.0 2732.6 Timm13 4352.4 7707.2 9340.0 Clpp 1163.1 2222.8 2527.5 Mrps7 1278.4 1905.2 2380.7 CEM 1 + Mrpl11 1418.2 2481.9 2951.4 Top 10 Genes Exosc4 795.1 1582.1 2025.0 C1qbp 3983.7 5391.8 5915.0 Phb2 4043.7 6400.7 7558.2 Naa10 2619.5 4224.4 5321.3

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21 GEO Series "GSE27379" 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=GSE27379 Status: Public on Dec 21 2011 Title: CD8+ T cell mediated lung inflammation Organism: Mus musculus Experiment type: Expression profiling by array Platform: GPL1261 Pubmed ID: 21518973 Summary & Design: Summary: Role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung.

Overall design: CD8+ T cell type comparison; lung disease state analysis

Background corr dist: KL-Divergence = 0.0455, L1-Distance = 0.0339, L2-Distance = 0.0016, Normal std = 0.6061

0.671 Kernel fit Pairwise Correlations Normal fit

Density 0.335

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

1 lung CL42 BLN activated CL43 BLN activated (0.161242)CL44 lung (naive) (0.289885) CL45 BLN (0.105793)(naive) SPC-HAxCL46 lung (0.236449) SPC-HAxCL4 (0.104453) (0.102177)[ min ] [ medium ] [ max ] CEM 1 Mrpl2 567.1 1058.3 2103.8 P ( S | Z, I ) = 1.00 Mrps10 732.7 1059.4 1640.8 Mean Corr = 0.63831 Mrpl46 800.2 1199.3 1750.1 Mrps34 669.0 1298.3 1891.4 Mrpl16 1455.4 1689.5 2419.7 Mrps23 308.5 420.1 639.1 Mrpl44 270.0 295.9 666.3 Mrps30 1228.8 1660.8 2040.1 Apex1 1010.4 1707.4 4595.0 Mrps27 53.7 181.4 399.0 Mrpl45 256.8 344.8 682.2 Rpl7l1 790.7 1068.1 1801.0 Mrpl4 886.6 1689.0 2493.5 Mrpl50 195.1 283.3 492.3 Mrpl54 182.3 258.8 364.8 Rps27l 578.3 716.6 2386.2 Qtrt1 315.6 697.8 746.9 Mrpl14 377.8 508.4 780.4 Rpl27 21287.2 28516.2 34823.3 Mrpl24 5116.0 6591.5 6901.5 Prmt3 1224.3 2543.6 2776.8 Mrpl12 532.9 976.9 2868.1 Stoml2 737.8 1154.5 2019.7 Timm13 1537.5 2313.3 4357.1 Clpp 744.5 943.0 1870.8 Mrps7 935.3 1136.5 1660.2 CEM 1 + Mrpl11 1167.5 1419.6 2808.0 Top 10 Genes Exosc4 202.2 382.0 625.7 C1qbp 823.6 3047.3 7432.2 Phb2 1302.5 2515.8 5421.9 Naa10 456.9 702.7 1548.9

Null module Serp1 Rps13 Rps7 Mettl17 Dnajc21 Rps18 Mrpl19 Canx Rps11 Mrpl33 Rps6kl1 Abcf1 Rps9 Mrpl38 Rps25 Srp68 Mrps5 Rps10 Rps17 Hspa14 Gcn1l1 Rpl3l Mrpl17 Mrpl21