Supplementary Information

Supplementary Materials and Methods

Multiple myeloma specimens

Primary bone marrow samples from 116 MM patients and 12 patients without tumors were obtained from the 4th Department of Internal Medicine, Hiroshima Atomic-Bomb

Survivors Hospital; the 1st Department of Internal Medicine, Sapporo Medical

University Hospital; and the Department of Hematology, Teine Keijinkai Hospital after acquisition of informed consent from each patient. Mononuclear cells were separated from 99 samples using Ficoll-Paque (StemCell Technologies), after which we separated the CD138-positive cells using CD138 MicroBeads (Miltenyi Biotec). There were five patients whose bone marrow specimens were collected before and after treatment. All five of those patients received treatment with Dex. Of those five patients, three received bortezomib and Dex; one received vincristine, adriamysin and Dex; and one received melphalan and Dex followed by peripheral blood stem cell transplantation.

Methylation analysis

Combined bisulfite restriction analysis (COBRA) were performed as described previously (1). The PCR products were digested with the restriction endonuclease Hinf

(TaKaRa) and precipitated with ethanol, after which the resultant DNA fragments were subjected to 2.5% agarose gel electrophoresis and stained with ethidium bromide.

Bisulfite-pyrosequencing was carried out as described previously (2). The primers used for COBRA were also used for pyrosequencing. After PCR, the biotinylated

PCR product was purified, made single-stranded, and used as a template in the pyrosequencing reaction. Briefly, the PCR products were bound to streptavidin sepharose beads HP (Amersham Biosciences), after which beads containing the immobilized PCR product were purified, washed, and denatured using a 0.2 mol/L

NaOH solution. After addition of 0.3 μmol/L sequencing primer to the purified PCR product, pyrosequencing was carried out using a PSQ96MA system (Biotage) and Pyro

Q-CpG software (Biotage). MM-related were deemed methylated if the level of methylation was above the 75th percentile level found in control bone marrow samples.

Statistics

Paired t tests were used to compare differences in methylation levels before and after treatments. Pearson’s and Spearman’s correlation coefficients (r and rs, respectively) were calculated to evaluate the correlation between expression levels

(log-transformed), fold expression levels, and methylation levels. Cell viability was assessed using one way ANOVA with post hoc Dunnett’s test. All statistical calculations were performed using SPSSJ 15.0 (SPSS Japan Inc.).

References.

1. Xiong Z, Laird PW. COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 1997; 25: 2532-4. 2. Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 2004; 32: e38.

Legends for Supplementary Figures.

Supplementary Figure 1.

Representative results of real-time PCR analysis of genes upregulated by DAC in MM cell lines. Expression levels of CST1 and IER3 relative to that in normal bone marrow are shown on the Y-axis.

Supplementary Figure 2.

Expression profile of candidate genes silenced by DNA methylation in MM. The heat map shows the expression profiles in normal colon, normal stomach and three cancer cell lines. Levels of expression are normalized to that in normal bone marrow.

Supplementary Figure 3.

Representative results of real-time PCR of candidate methylation target genes in MM cell lines treated with DAC.

Supplementary Figure 4.

Summary of gene expression in MM cells treated with DAC. Levels of expression are normalized to those in mock treated cells.

Supplementary Figure 5.

Bisulfite-sequencing analysis of BNIP3 and SOCS3 in MM cell lines. Open circles indicate the unmethylated CpG sites; filled circles indicate the methylated CpG sites.

Supplementary Table 1. Primer sequences and restriction enzymes used in this study. Primer Gene name Forward Reverse Restriction enzymes COBRA GPR30 GGTYGAGTGTTTTTGGAGGT CCTTTATCCRCTAAATATAAATAATAC TaqI FMR1NB GTTAYGGATTGTTTTGGAAG TTACCAACTCTAAATAAACCACAC MboI CST6 TTYGAGTTTYGTTTTAGTTTTAGGT TAACAACRCCAAAAAACAAAATAC HhaI TNFRSF4 TAYGGTGTTTAGTTTTAGGTTTAGGAGATCCCCRACCTACCACCTTC TaqI SECTM1 GGAGTTTTAGGAAAATGAAAG CCCRTAAAAATAATAAATTCAC HhaI PTRF AGYGGGAGATTYGGAGAGAAGT CCTCCCTTTCTAAAATAAAACCAACC TaqI C16orf30 TTTTTGTTGAGAGTTAGGGAAG ACACCRACCTACTATAAATACCA MboI RASD1 GTTTTTAGTTTTAGTTYGATTTTGGA CCRCCCTTATATACAACCTACTC AfaI DAZL TGAAGAGAAAAGGAAAATTAAGAG AAACRCTACCACCCATTAAC TaqI DDX43 TAATGGTTGYGTGAAATTAGTG CCTCCRTAATAAAACATTATTCC MluI PDIA2 GGTTTTGTTTTTGTTGGGATTG AAATTTCCTCCTCTAAAAACTCCTC MluI FES TTYGGGGTTTGGGTTAATTG ACRCCTACTCTACCCCTACCTAC TaqI COX7A1 GTTTTAGTTTYGTYGYGTTTTTAG AACCCAACCCATAAAAACCTCA TaiI KRTCAP3 GGGGTYGGGTTTAGGTATAG CACRAAAAAAAACAAAATTAAATC HhaI RRAD TTGAGAAGGYGGTGGTTGTAGTAGTACCRAAACCCCTCCRAACCTAA TaqI FGFR3 GGGGTYGGGAYGTAGGAGT RCAAACAAAAACRCCCATAAC TaqI IER3 GYGTTTAGGATTGTGTATGTTAAGT TAAACCRAACRAAATATAAAACCA TaqI TKTL1 ATATTTTAGATTTTTTGATTTGTTTG TTAAAATCTAAAAACCCACTCCT TaqI CMTM3 GGTGGTTAAGAAAGTYGTAAGAAA CCACCCRTCTACCCCTATC MluI SYT11 GYGGAGTTTATTTTTTATTAGGA CTCTAAAAACCCTCRATCAATAC MboI P2RY6 GGATTTTAGYGGTGYGGAG CAACTAATCCRACCCAAATATCACT TaiI GDF15 TTTAGAGTYGTAATTTGTATAGTTATGTCRAAATACAACTCTAAAAATCC TaqI

RASD1 pyro-seq1GYGTTTAGAGAGTAGGAGTT

Bisulfite-sequencing BNIP3 GATATGGYGTTAGAGGGTAATTG CCCRCCCTACCCTATAAATTC

SOCS3 GTTTTTTTTTGTTGYGAGTAGTGAT CRTCCCTCRAACTTCCCCT

ABL1 TTGGTTYGGGTTGGTTTTGGAAAG AAACCRAAACCCCTCTCCCAACTC Y=C or T, R=G or A

12/26/20083:09 AM Supplementary Table 2. Genes up-rehulated by DAC in KMS12PE. Gene Name Systematic Name DAC VIM NM_003380 181.2 TNFRSF4 NM_003327 113.0 GPR30 NM_001505 85.6 VASN NM_138440 78.6 CST6 NM_001323 63.7 FMR1NB NM_152578 46.1 CKM NM_001824 45.1 AIF1 NM_004847 44.5 COX7A2 NM_001865 44.0 CMTM3 NM_144601 38.5 GPR68 NM_003485 35.9 VIM NM_003380 35.3 LOC645277 XM_928321 32.0 RAB13 NM_002870 31.7 TAS1R1 NM_138697 31.2 EDNRB NM_003991 30.4 B3GALT4 NM_003782 28.9 CXCL9 NM_002416 28.5 PLAT NM_000930 27.5 CCRL2 NM_003965 27.5 TNFAIP2 NM_006291 27.4 ACRC NM_052957 26.1 LAG3 NM_002286 25.8 A_24_P177634 A_24_P177634 24.6 C16orf30 NM_024600 24.4 THC2333719 THC2333719 23.7 MYO1G NM_033054 23.1 ID2 NM_002166 22.8 M32220 M32220 22.7 P2RY5 NM_005767 22.5 SECTM1 NM_003004 20.7 GPX1 NM_201397 20.6 IFI27 NM_005532 19.8 CCR9 NM_006641 19.4 PEPP-2 NM_032498 18.9 ART3 NM_001179 18.8 IFI27 NM_005532 18.1 ENST00000371388 ENST00000371388 18.0 APOE NM_000041 17.6 PTRF NM_012232 17.4 CHRDL2 NM_015424 17.4 CLDN19 NM_148960 17.3 HAS3 NM_005329 17.0 EPHA2 NM_004431 17.0 THC2337710 THC2337710 17.0 LGALS8 NM_006499 16.9 SPINT1 NM_003710 16.5 IFI27 NM_005532 16.5 ZP1 NM_207341 16.3 LOC440335 BC022385 16.2 THC2373524 THC2373524 15.7 AGMAT NM_024758 15.6 CDKN1C NM_000076 15.3 TNF NM_000594 15.1 CYB5R2 NM_016229 15.0 IFI27 NM_005532 14.9 IFI27 NM_005532 14.8 IFI27 NM_005532 14.8 IFI27 NM_005532 13.8 BTBD14A NM_144653 13.8 CCR7 NM_001838 13.5 TMEM49 BC024020 13.5 AGXT2L1 NM_031279 13.4 ANGPT2 NM_001147 13.4 IFI27 NM_005532 13.4 NGB NM_021257 13.2 CNDP1 NM_032649 13.1 IFI27 NM_005532 13.1 AHNAK NM_001620 13.1 RAMP1 NM_005855 13.0 BM045853 BM045853 12.9 ICOS NM_012092 12.8 RUNX3 NM_004350 12.6 LXN NM_020169 12.2 SYT11 NM_152280 12.2 RPGRIP1 NM_020366 12.2 IFI27 NM_005532 12.2 TNNC2 NM_003279 12.1 FLJ25410 NM_144605 11.9 GLULD1 NM_016571 11.9 MET NM_000245 11.8 PROC NM_000312 11.7 A_24_P478940 A_24_P478940 11.3 ENST00000381781 ENST00000381781 11.2 GPR56 NM_201525 11.0 SPINT2 NM_021102 11.0 GNG11 NM_004126 11.0 PLXND1 NM_015103 11.0 BC036938 BC036938 10.9 RASD1 NM_016084 10.9 FARP1 NM_005766 10.8 P2RY6 NM_176798 10.7 LEFTY1 NM_020997 10.6 CD52 NM_001803 10.6 GDF15 NM_004864 10.5 A_24_P109661 A_24_P109661 10.4 A_23_P15226 A_23_P15226 10.4 ENST00000320378 ENST00000320378 10.3 VCX2 NM_016378 10.2 WBP5 NM_016303 10.2 KITLG NM_000899 10.1 RHBDL3 NM_138328 10.0 THC2383841 THC2383841 10.0 Supplementary Table 3. Genes up-regulated by DAC in RPMI8226. Gene Name Systematic Name DAC GPR30 NM_001505 217.7 FMR1NB NM_152578 191.1 DAZL NM_001351 187.0 DDX43 NM_018665 185.0 BC036938 BC036938 121.7 GSTP1 NM_000852 110.9 CST6 NM_001323 89.8 THC2376729 THC2376729 77.7 VCX3A NM_016379 76.9 VCX NM_013452 72.5 VCX2 NM_016378 72.4 THC2407823 THC2407823 67.8 SYCP3 NM_153694 64.5 NEFH NM_021076 62.6 PAGE2 NM_207339 61.7 VASN NM_138440 58.8 CXCL9 NM_002416 57.5 TNFRSF4 NM_003327 57.0 PRAME NM_206956 55.4 PDIA2 NM_006849 54.0 CKM NM_001824 51.4 PAGE5 NM_130467 49.2 DAZ2 NM_001005785 45.5 A_24_P7750 A_24_P7750 44.5 XIST NR_001564 41.3 UCHL1 NM_004181 39.3 BM668321 BM668321 38.2 ENST00000370363 ENST00000370363 38.2 CNDP1 NM_032649 37.6 ECAT8 AK023134 37.2 LEFTY1 NM_020997 36.9 ENST00000311695 ENST00000311695 36.6 MXRA8 NM_032348 35.6 TAS1R1 NM_138697 34.6 RTP3 NM_031440 34.5 BEX1 NM_018476 33.2 CARD9 NM_052813 32.0 KRT19 NM_002276 31.8 LGALS2 NM_006498 31.7 IL18 NM_001562 31.6 FES NM_002005 30.7 RAB7B NM_177403 30.2 CD52 NM_001803 29.9 CPLX3 NM_001030005 29.6 AIF1 NM_004847 28.7 P2RY5 NM_005767 27.8 A_23_P15226 A_23_P15226 27.6 VCY NM_004679 27.6 SECTM1 NM_003004 27.2 ART3 NM_001179 27.0 FAM26A NM_182494 26.9 CDH1 NM_004360 26.3 THC2304038 THC2304038 25.1 LAG3 NM_002286 24.8 CYB5R2 NM_016229 24.3 COX7A1 NM_001864 24.2 CNN3 NM_001839 24.2 GPR68 NM_003485 23.9 VCX2 NM_016378 23.0 THC2437822 THC2437822 22.4 THC2333719 THC2333719 22.2 LY6K NM_017527 22.1 C8G NM_000606 21.9 LOC643431 XM_928128 21.0 DMRTB1 NM_033067 20.8 A_32_P112546 A_32_P112546 20.7 CGREF1 NM_006569 20.0 CCRL2 NM_003965 19.7 PPAPDC3 NM_032728 19.3 A_24_P401124 A_24_P401124 19.3 ACRC NM_052957 18.5 MYO1G NM_033054 18.4 RRP22 NM_001007279 18.3 RP13-36C9.6 NM_001007551 18.2 DNALI1 NM_003462 17.9 HORMAD1 NM_032132 17.9 HSD17B1 NM_000413 17.7 CATSPER1 NM_053054 17.6 FLJ10324 NM_018059 17.5 CRYAA NM_000394 17.4 TEKT2 NM_014466 17.2 APOC1 NM_001645 16.9 PKP3 NM_007183 16.8 A_24_P745352 A_24_P745352 16.8 PTRF NM_012232 16.5 KRTCAP3 AY358993 16.4 MAEL NM_032858 16.3 CRYBA4 NM_001886 16.2 RAMP1 NM_005855 16.1 NDRG4 NM_022910 15.9 ENST00000353250 ENST00000353250 15.8 SMARCA1 NM_003069 15.6 A_24_P195974 A_24_P195974 15.4 RP4-742C19.3 NM_181773 15.4 RGS1 NM_002922 15.3 FAM9C NM_174901 15.0 BCNP1 NM_173544 15.0 SERPINF1 NM_002615 14.6 RAB13 NM_002870 14.5 MMP13 NM_002427 14.2 PTGER1 NM_000955 14.1 C6orf154 NM_001012974 14.0 S100A16 NM_080388 13.8 RRAD NM_004165 13.7 KRTCAP3 NM_173853 13.7 C16orf30 NM_024600 13.6 CR613736 CR613736 13.6 DNMT3L NM_013369 13.4 A_24_P93111 A_24_P93111 13.2 RAB34 NM_031934 12.8 LOC285401 AK091178 12.7 LTK NM_002344 12.7 FGFR3 NM_000142 12.6 TMEM49 BC024020 12.6 RARRES2 NM_002889 12.6 RRAD NM_004165 12.6 IER3 NM_003897 12.4 BCL2A1 NM_004049 12.3 ROBO3 NM_022370 12.3 BEX2 NM_032621 12.3 RBMY1B NM_001006121 12.2 EDG6 NM_003775 12.2 A_24_P341546 A_24_P341546 12.2 TKTL1 NM_012253 12.1 CLIC3 NM_004669 12.0 FAM9C NM_174901 11.9 KRT8 NM_002273 11.8 PIWIL2 NM_018068 11.7 THC2312585 THC2312585 11.7 ZNF502 NM_033210 11.5 TNF NM_000594 11.4 C21orf105 BC005107 11.3 ALDOB NM_000035 11.3 A_24_P281605 A_24_P281605 11.2 A_24_P418216 A_24_P418216 11.2 A_24_P844100 A_24_P844100 11.1 HSPA1A NM_005345 11.1 ATP4B NM_000705 11.0 ADAM8 NM_001109 10.9 COL8A2 NM_005202 10.9 MTMR11 NM_181873 10.8 CXCL1 NM_001511 10.8 ENST00000267857 ENST00000267857 10.6 CLDN4 NM_001305 10.5 LOC400751 BC031250 10.5 HSD11B1 NM_181755 10.4 SPOCK2 NM_014767 10.3 CRYAA NM_000394 10.2 RAB25 NM_020387 10.2 FRG2 NM_001005217 10.2 EMILIN2 NM_032048 10.2 THC2414226 THC2414226 10.1 FBLIM1 NM_017556 10.1 KRT8 NM_002273 10.1 Supplementary Table 4. Genes up-regulated by DAC and/or Dex in OPM1. Gene Name Systematic Name Dex DAC Dex+DAC SSTR2 NM_001050 1.1 1.5 15.0 THC2656116 THC2656116 1.1 1.1 15.0 MAP9 NM_001039580 1.1 1.3 14.6 ADAMTS12 NM_030955 1.1 1.1 14.3 NEFL NM_006158 1.1 1.1 14.0 BNIP3 NM_004052 1.9 2.1 14.0 PPP1R2P9 NR_002191 1.1 1.3 13.8 CXCL13 NM_006419 1.4 1.1 13.8 CX3CL1 NM_002996 1.1 1.1 13.7 KIAA2022 NM_001008537 1.1 1.1 13.2 PARP12 NM_022750 1.1 1.1 12.8 CHST2 NM_004267 1.7 1.7 12.5 MLLT4 BC014505 2.0 1.2 12.3 THC2660651 THC2660651 1.1 1.1 12.1 RNF43 NM_017763 1.1 1.5 12.1 AQP9 NM_020980 1.1 1.1 11.9 CYR61 NM_001554 1.1 1.4 11.5 VCAM1 NM_001078 1.1 1.1 11.0 THC2668815 THC2668815 1.1 1.1 10.9 BAIAP2L2 AK026235 1.1 1.2 10.9 RAB31 NM_006868 1.1 1.1 10.7 PCSK9 NM_174936 1.1 1.4 10.6 CD109 NM_133493 1.1 1.4 10.5 TRAM1L1 NM_152402 1.1 1.5 10.3 AY358804 AY358804 1.1 1.1 10.3 THC2662240 THC2662240 1.1 1.4 10.2 LOC387763 ENST00000339446 1.3 1.6 10.2 LOC441052 AF131741 1.1 1.1 10.1 CMTM3 NM_144601 1.1 1.1 10.0 NLRP7 NM_139176 1.1 1.1 9.9 LILRB2 NM_005874 1.1 1.1 9.9 TMEM16A NM_018043 1.1 1.1 9.8 GNA12 NM_007353 1.6 1.6 9.8 PRRX2 NM_016307 1.1 1.1 9.8 CAPSL NM_144647 1.1 1.1 9.6 FILIP1L NM_182909 1.1 1.1 9.6 PSG3 NM_021016 1.1 1.1 9.6 BEX1 NM_018476 1.1 1.1 9.5 KIF26B NM_018012 1.1 1.5 9.4 TDRD6 NM_001010870 1.1 1.1 9.4 MYH6 NM_002471 1.1 1.1 9.0 DB090170 DB090170 1.1 1.2 8.9 REN NM_000537 1.1 1.1 8.8 AK001829 AK001829 1.1 1.1 8.7 INSAF S73205 1.1 1.1 8.6 CLDN19 NM_148960 1.1 1.3 8.5 IGFL2 NM_001002915 2.5 1.7 8.4 ARHGAP24 AK130576 1.9 1.6 8.3 AK096803 AK096803 1.1 1.1 8.2 AIF1 NM_004847 0.9 1.0 8.2 SLC35D2 NM_007001 1.7 1.1 8.1 SPIN3 NM_001010862 1.1 1.5 8.1 TMEM45A NM_018004 1.1 1.1 8.0 ZNF643 NM_023070 2.3 1.7 8.0 DLK1 NM_003836 1.1 1.1 7.8 HNRNPG-T NM_014469 1.0 1.3 7.8 MAP9 NM_001039580 2.0 0.9 7.8 C1orf115 NM_024709 1.3 1.2 7.7 BMPER NM_133468 1.1 1.1 7.7 MYF6 NM_002469 1.1 1.1 7.7 AF090944 AF090944 1.2 1.3 7.6 DLEC1 NM_007335 1.1 1.4 7.6 ENO2 NM_001975 1.1 1.1 7.5 RAB6IP1 NM_015213 1.1 1.1 7.5 KCNS1 NM_002251 1.3 1.5 7.5 BCL7A NM_020993 1.1 1.2 7.4 BU624603 BU624603 2.7 1.6 7.4 FN1 NM_212482 1.1 1.1 7.3 DMKN NM_033317 1.1 1.1 7.2 FLRT3 NM_198391 1.1 1.1 7.2 MYO7A NM_000260 0.9 0.8 7.1 ATP1A4 AK098076 1.1 1.1 7.1 FGFBP2 NM_031950 1.1 1.4 7.1 LOC400794 BC020945 1.1 1.1 7.0 ENST00000359743 ENST00000359743 1.3 1.1 7.0 RETN NM_020415 1.1 1.4 7.0 S100A14 NM_020672 1.1 1.1 7.0 C20orf186 NM_182519 0.8 1.0 6.9 EFEMP1 NM_004105 1.1 1.1 6.9 DENND2C CR749576 1.2 1.1 6.8 ALOX5 NM_000698 1.1 1.3 6.8 LGALS8 NM_006499 1.1 1.1 6.7 THC2676504 THC2676504 1.4 1.1 6.6 AI859463 AI859463 1.5 1.0 6.6 CYP4B1 NM_000779 1.1 1.2 6.6 RAB31 NM_006868 1.1 1.1 6.6 SEPT10 NM_144710 1.1 1.1 6.5 MPN2 NM_183062 1.7 1.1 6.4 BC037919 BC037919 1.6 1.1 6.4 KIF7 NM_198525 1.1 1.1 6.4 CTSL2 NM_001333 1.1 1.1 6.4 RTP3 NM_031440 1.1 1.1 6.4 ELL3 NM_025165 1.1 1.2 6.3 A_24_P500186 A_24_P500186 1.1 1.1 6.2 APOC4 NM_001646 1.1 1.3 6.2 ZNF480 NM_144684 1.1 1.1 6.2 PPM1J NM_005167 1.1 1.4 6.2 CRISP2 NM_003296 1.1 1.1 6.2 HERC5 NM_016323 1.1 1.1 6.2 NUDT10 NM_153183 1.1 1.3 6.2 A_23_P11119 A_23_P11119 1.1 1.3 6.2 BCL2L10 NM_020396 1.1 1.3 6.1 NAP1L5 NM_153757 1.1 1.1 6.0 PDLIM3 NM_014476 1.1 1.1 6.0 STAR NM_000349 1.1 1.1 6.0 A_32_P159528 A_32_P159528 1.1 1.1 6.0 KLHL5 NM_015990 1.1 1.4 6.0 TTC28 AK092338 1.0 0.9 6.0 ATP9A NM_006045 1.1 1.1 5.9 ROS1 NM_002944 1.1 1.1 5.9 KRT18P40 XR_017288 1.1 1.1 5.9 THC2754547 THC2754547 1.1 1.3 5.9 FLJ40473 AK097792 1.2 1.1 5.8 ADAMTS7 AF140675 1.1 1.1 5.8 LOC730704 XM_001128267 1.1 1.4 5.8 FHOD3 NM_025135 0.9 0.8 5.7 PHLDA2 NM_003311 1.1 1.2 5.7 PCDH7 NM_002589 1.1 1.1 5.6 BC034306 BC034306 1.1 1.1 5.6 AF118069 AF118069 1.1 1.1 5.6 NEU4 NM_080741 1.5 1.1 5.6 SERPINB3 NM_006919 1.1 1.1 5.6 GPX2 NM_002083 1.0 1.1 5.6 C6orf10 NM_006781 1.0 0.9 5.6 PCDH12 NM_016580 1.1 1.1 5.6 THC2728570 THC2728570 1.1 1.5 5.5 COL20A1 NM_020882 1.1 1.1 5.5 UNC45B NM_173167 1.1 1.4 5.5 DMD NM_004019 1.1 1.1 5.5 AF130074 AF130074 1.1 1.1 5.5 NDN NM_002487 1.1 1.1 5.4 CPVL NM_031311 1.4 1.1 5.4 DLX4 NM_138281 1.1 1.1 5.4 THC2535767 THC2535767 1.5 1.0 5.4 TSPAN6 NM_003270 1.1 1.1 5.4 ALX4 NM_021926 1.1 1.1 5.4 ZFP2 NM_030613 1.1 1.2 5.4 G0S2 NM_015714 1.1 1.1 5.4 THC2641484 THC2641484 1.0 1.6 5.3 EID3 NM_001008394 0.9 1.2 5.3 A_24_P878376 A_24_P878376 1.1 1.5 5.3 ID4 NM_001546 1.1 1.1 5.3 FMN2 NM_020066 1.1 1.8 5.3 SLC16A5 NM_004695 1.1 1.1 5.3 THC2753798 THC2753798 1.1 1.9 5.3 PTPN20B NM_015605 1.1 1.1 5.3 DNAJB8 NM_153330 1.1 1.1 5.2 PAPSS2 NM_001015880 1.1 1.9 5.2 PDGFA NM_002607 1.1 1.6 5.2 LAD1 NM_005558 1.1 1.5 5.2 FLJ39609 AK096928 1.1 1.1 5.2 PTN NM_002825 1.1 1.9 5.2 KCNIP3 NM_013434 1.1 1.1 5.2 A_24_P654255 A_24_P654255 1.1 1.1 5.1 HSD3B1 NM_000862 1.3 1.1 5.1 KIAA1466 AB040899 1.1 1.8 5.1 LOC349196 AK090418 1.0 2.9 5.1 THC2616992 THC2616992 1.1 1.1 5.1 DKFZP686A01247 NM_014988 1.1 1.2 5.1 PDCL2 NM_152401 1.1 1.4 5.1 SLC2A2 NM_000340 1.1 1.1 5.0 CYP2C9 NM_000771 1.1 1.3 5.0 ELF5 NM_198381 1.1 1.1 5.0 PHC2 NM_198040 1.1 1.1 5.0 NXPH3 AB032985 1.1 1.1 5.0 DNAJA4 NM_018602 1.1 1.5 5.0 LEPREL1 NM_018192 1.1 1.1 5.0 USHBP1 NM_031941 1.1 1.4 5.0 IRX2 ENST00000302057 1.1 1.5 5.0 FAM9C BX648919 1.3 1.2 5.0 A_32_P149625 A_32_P149625 0.8 1.1 5.0 SORBS2 NM_021069 1.1 1.1 5.0 A_24_P941450 A_24_P941450 1.1 1.1 5.0 RPESP NM_153225 1.5 0.8 5.0 MAK NM_005906 1.2 1.9 5.0 THC2573284 THC2573284 1.1 1.2 5.0 CD19 NM_001770 1.1 1.2 4.9 NPY NM_000905 1.0 1.6 4.9 PAQR5 NM_017705 0.9 1.3 4.9 AW971282 AW971282 1.1 1.1 4.9 CDH19 NM_021153 1.1 1.5 4.9 ENST00000379528 ENST00000379528 1.1 1.1 4.9 A_24_P736853 A_24_P736853 1.1 1.1 4.9 THC2651178 THC2651178 1.0 3.0 4.9 THC2661012 THC2661012 1.1 1.6 4.9 COLQ NM_080542 1.1 1.8 4.9 DNAJA4 AF116663 1.1 1.1 4.9 CMBL NM_138809 1.0 2.8 4.8 C10orf47 NM_153256 0.9 2.6 4.8 SEPSECS NM_153825 1.1 2.0 4.8 BC065757 BC065757 1.1 2.0 4.8 THC2716178 THC2716178 1.1 1.1 4.8 FAM92A3 BC059396 1.1 1.9 4.8 ENST00000370378 ENST00000370378 1.1 1.3 4.8 THC2669541 THC2669541 1.1 1.1 4.8 ZNF750 NM_024702 1.5 1.1 4.7 THC2608967 THC2608967 1.1 1.1 4.7 AA514833 AA514833 1.1 1.1 4.7 DQ168992 DQ168992 1.1 1.1 4.7 KIAA1279 NM_015634 2.2 1.1 4.7 FLJ13231 NM_023073 1.0 2.8 4.7 PENK NM_006211 0.9 0.8 4.7 EIF5A2 NM_020390 1.0 2.9 4.7 OR7E91P NR_002185 1.0 3.1 4.7 FBP2 NM_003837 1.1 1.2 4.7 NPTX1 NM_002522 1.1 1.7 4.7 TCL6 NM_020552 1.1 1.8 4.7 C9orf70 BC007366 1.1 1.1 4.7 PROS1 NM_000313 1.1 1.9 4.7 A_24_P636974 A_24_P636974 0.9 2.7 4.7 BC029602 BC029602 1.1 1.1 4.7 IL7R NM_002185 2.1 1.2 4.6 CRB1 NM_201253 1.1 1.4 4.6 RAPGEF2 AL117397 1.2 1.4 4.6 CCL25 NM_005624 0.7 1.6 4.6 C18orf2 AF295728 1.1 1.4 4.6 DB295730 DB295730 1.1 1.1 4.6 FLJ30679 AK055241 1.1 1.1 4.6 THC2614840 THC2614840 1.4 1.3 4.6 ARNTL2 AF256215 1.1 1.1 4.6 ENST00000374860 ENST00000374860 1.0 2.9 4.6 TEX14 NM_198393 1.3 1.5 4.6 BC038719 BC038719 1.1 1.1 4.6 THC2637155 THC2637155 1.3 1.4 4.6 BC032041 BC032041 1.1 1.1 4.6 FLJ22536 AK022865 0.9 2.7 4.6 C1QTNF3 AK094895 1.1 1.9 4.6 MARK1 NM_018650 1.2 1.8 4.6 TMEM185B NR_000034 1.1 1.6 4.6 APOBEC2 NM_006789 1.1 1.1 4.5 RP5-821D11.2 NM_152513 1.1 1.1 4.5 TRPM4 NM_017636 1.1 1.8 4.5 HGFAC NM_001528 1.1 1.2 4.5 HOP NM_139211 1.1 1.7 4.5 A_24_P739785 A_24_P739785 1.1 1.8 4.5 SPAG6 NM_172242 1.0 1.4 4.5 INSM1 NM_002196 1.1 1.4 4.5 THC2651722 THC2651722 1.1 1.6 4.5 THC2706230 THC2706230 1.2 1.7 4.5 C19orf31 NM_001014373 0.7 1.7 4.5 PPP4R1L NM_018498 1.1 1.1 4.5 AK095439 AK095439 1.1 1.6 4.5 KCNB2 NM_004770 1.3 1.8 4.5 AUTS2 BC011643 1.1 1.1 4.5 BC017937 BC017937 1.3 1.6 4.5 TCF15 NM_004609 1.1 1.6 4.5 PTGIR NM_000960 1.1 1.7 4.4 ZSCAN18 NM_023926 0.9 2.7 4.4 A_24_P919825 A_24_P919825 1.1 1.1 4.4 ANKS6 NM_173551 1.1 1.3 4.4 FOXF1 NM_001451 0.9 1.5 4.4 AF318318 AF318318 1.1 1.1 4.4 MOSC1 NM_022746 1.1 1.1 4.4 ACTN2 NM_001103 1.1 1.1 4.4 PHLDA1 NM_007350 1.1 1.1 4.4 OR2B6 NM_012367 0.6 0.6 4.4 ESRRG NM_206594 1.1 1.3 4.4 AMIGO1 NM_020703 1.1 1.1 4.4 CACNB2 AK128769 1.1 1.6 4.4 ENST00000358162 ENST00000358162 0.8 1.1 4.4 THC2730567 THC2730567 1.1 1.2 4.4 PHACTR1 AB051520 1.1 1.1 4.4 NFE2 NM_006163 1.1 1.1 4.4 FGFBP1 NM_005130 1.1 1.1 4.4 MOCS1 NM_138928 1.1 2.0 4.4 CHRNG NM_005199 1.1 1.1 4.3 DTX4 ENST00000227451 1.1 1.8 4.3 COL6A1 NM_001848 0.7 1.7 4.3 ENST00000389477 ENST00000389477 1.1 1.9 4.3 THC2781239 THC2781239 1.1 1.6 4.3 LOC650177 XR_018734 1.4 1.5 4.3 MAOA NM_000240 0.6 1.5 4.3 LOXL4 NM_032211 1.1 1.1 4.3 TAC1 NM_003182 1.1 1.1 4.3 PARP3 NM_001003935 0.9 2.8 4.3 SYT11 NM_152280 1.1 1.5 4.3 HSPA12B NM_052970 1.1 1.1 4.3 SLC4A4 NM_003759 1.0 2.8 4.3 BC017937 BC017937 1.2 1.5 4.3 DSP NM_004415 1.1 1.1 4.3 TDRD10 NM_182499 1.1 1.2 4.3 hCG_2036596 AK124708 1.1 1.1 4.3 TNFAIP8L3 NM_207381 0.9 1.5 4.2 ZFP14 NM_020917 1.3 1.6 4.2 HIST1H2AK BC034487 1.1 1.9 4.2 A_32_P191141 A_32_P191141 1.1 1.9 4.2 FCER1A NM_002001 1.1 2.0 4.2 ENST00000327299 ENST00000327299 1.1 2.0 4.2 SYNGAP1 NM_006772 1.2 1.5 4.2 AW445156 AW445156 1.1 1.9 4.2 CRIP3 NM_206922 1.1 1.1 4.2 PHLDA1 NM_007350 1.0 1.2 4.2 NPNT NM_001033047 1.1 1.1 4.2 LTB4DH NM_012212 1.1 1.1 4.2 ADAMTS3 NM_014243 1.1 1.9 4.2 THC2668923 THC2668923 0.8 1.4 4.2 KAZALD1 ENST00000224809 1.3 2.0 4.2 RASD1 NM_016084 0.9 1.4 4.2 DKFZP434P211 AL117401 1.5 1.3 4.2 C10orf25 NM_001039380 1.1 1.8 4.2 AK129542 AK129542 1.7 1.1 4.2 A_32_P116088 A_32_P116088 0.7 1.4 4.2 THC2657554 THC2657554 1.1 1.1 4.2 A_24_P384604 A_24_P384604 1.1 1.1 4.2 GLYAT NM_201648 1.1 1.1 4.1 PSG6 NM_002782 1.1 1.3 4.1 LRRC49 NM_017691 0.7 1.7 4.1 MGC13053 BC006134 1.1 1.8 4.1 KRT83 NM_002282 1.1 1.1 4.1 A_32_P55438 A_32_P55438 0.7 1.7 4.1 ARHGAP28 NM_001010000 1.1 1.6 4.1 GFRA1 NM_005264 1.1 1.1 4.1 ENST00000254109 ENST00000254109 1.1 1.1 4.1 GRAMD1B AY358924 1.1 1.5 4.1 FGFR2 NM_022970 1.2 1.7 4.1 LOC441601 NR_003034 1.1 1.1 4.1 GDF9 NM_005260 1.6 1.1 4.1 MOBKL2B NM_024761 1.1 1.6 4.1 SPG3A NM_015915 0.9 1.6 4.1 KIAA2022 NM_001008537 1.1 1.1 4.1 BC017937 BC017937 1.3 1.5 4.1 A2M NM_000014 1.1 1.6 4.1 C3orf41 AL117530 1.1 1.1 4.1 PRRG3 NM_024082 1.1 2.0 4.1 FMN2 NM_020066 1.1 1.1 4.0 THC2667273 THC2667273 1.7 1.1 4.0 AK093987 AK093987 1.1 1.1 4.0 C1orf51 NM_144697 1.1 2.1 4.0 ENST00000356186 ENST00000356186 1.1 1.8 4.0 REG1A NM_002909 1.1 1.5 4.0 NEURL NM_004210 0.7 1.1 4.0 A_32_P99744 A_32_P99744 1.1 1.9 4.0 LOC441258 AK024602 1.2 1.9 4.0 LOC54103 AK126364 1.1 1.6 4.0 IL18R1 NM_003855 1.1 1.7 4.0 THC2591546 THC2591546 1.1 1.6 4.0 ANKRD6 NM_014942 1.1 1.1 4.0 A_32_P147395 A_32_P147395 1.1 1.1 4.0 AW817085 AW817085 1.1 1.6 4.0 THC2682319 THC2682319 1.1 1.6 4.0 THC2686110 THC2686110 1.1 2.0 4.0 PBLD NM_022129 1.1 1.7 4.0 PRKCZ NM_002744 1.2 1.8 4.0 PDE4DIP NM_022359 1.1 1.1 4.0 MGC16275 BC043607 1.1 1.8 4.0 BX102475 BX102475 0.7 1.5 3.9 THC2684461 THC2684461 1.1 1.1 3.9 EBF3 NM_001005463 1.1 1.1 3.9 LOC390705 BC041879 1.1 1.3 3.9 THC2670311 THC2670311 1.1 1.4 3.9 LOC131873 AL713792 1.1 1.9 3.9 DAG1 NM_004393 1.3 1.6 3.9 THC2519174 THC2519174 1.1 1.1 3.9 AW664702 AW664702 1.1 1.1 3.9 LOC400752 ENST00000372127 1.3 1.1 3.9 NEFL NM_006158 0.6 0.5 3.9 FLJ33790 NM_001039548 1.0 1.7 3.9 CTTN NM_005231 0.9 0.9 3.9 MMP13 NM_002427 1.1 1.1 3.9 PCDHGB4 NM_032098 1.1 1.5 3.9 HS3ST3A1 NM_006042 1.1 1.1 3.9 AK124399 AK124399 1.1 1.1 3.9 THC2646374 THC2646374 1.2 1.1 3.9 TPCN2 AL137479 1.4 1.3 3.9 THC2500744 THC2500744 1.4 1.4 3.9 THC2672319 THC2672319 1.1 1.1 3.9 TRIM50 NM_178125 1.1 1.5 3.9 DHX34 D50924 1.0 1.5 3.9 AL049991 AL049991 1.1 1.6 3.9 DMD NM_004023 1.1 1.1 3.8 LOC642413 XR_016155 1.1 1.1 3.8 ELSPBP1 NM_022142 1.1 1.1 3.8 ALDOB NM_000035 0.8 1.5 3.8 GATA4 AF318320 1.1 1.6 3.8 ANGPT2 ENST00000382726 1.4 1.4 3.8 KIAA1841 BC039298 1.1 1.7 3.8 FLJ13224 AK023286 1.2 1.1 3.8 AK021427 AK021427 1.1 1.1 3.8 GPR109B NM_006018 1.1 1.1 3.8 TCF7 NM_003202 1.1 1.3 3.8 RAPH1 NM_025252 0.7 1.3 3.8 ENST00000318093 ENST00000318093 1.1 1.8 3.8 A_24_P874334 A_24_P874334 1.5 1.3 3.8 CEACAM19 AK128234 1.0 1.9 3.8 KLRF1 NM_016523 1.1 1.1 3.8 CTDSPL NM_001008392 1.1 1.1 3.8 NO145 NM_001040274 1.1 1.1 3.8 THC2558594 THC2558594 1.1 1.2 3.8 C22orf31 NM_015370 1.1 1.1 3.8 ENST00000332432 ENST00000332432 1.1 1.3 3.8 LOC220115 NR_002793 1.1 1.6 3.8 CBR4 AK027337 1.3 1.3 3.8 BC019241 BC019241 1.1 1.7 3.8 FABP3 NM_004102 1.1 1.1 3.8 A_23_P145596 A_23_P145596 1.6 1.3 3.8 A_24_P928830 A_24_P928830 1.1 1.1 3.8 TKTL2 NM_032136 1.1 1.1 3.8 FAM110B NM_147189 1.3 1.4 3.8 THC2661011 THC2661011 1.1 1.6 3.8 FCAMR AY063125 0.6 0.8 3.8 A_32_P72682 A_32_P72682 1.1 1.3 3.8 DEFB104A NM_080389 1.1 1.1 3.7 KIAA1598 NM_018330 1.1 1.1 3.7 A_32_P13202 A_32_P13202 1.1 1.3 3.7 ABL1 NM_005157 1.4 1.4 3.7 A_24_P384119 A_24_P384119 1.1 1.4 3.7 LOC339240 NR_001443 1.1 1.3 3.7 TMEM132A NM_017870 1.2 1.1 3.7 AK128756 AK128756 1.1 1.6 3.7 ENST00000390369 ENST00000390369 1.1 1.1 3.7 ADAMTS18 NM_139054 1.1 1.1 3.7 KCNH5 NM_172376 1.1 1.1 3.7 AK055112 AK055112 1.1 1.1 3.7 THC2636507 THC2636507 1.1 1.4 3.7 DA727827 DA727827 1.1 1.4 3.7 PDCD4 NM_145341 0.8 1.8 3.7 NRSN1 NM_080723 1.1 1.1 3.7 NR1H4 NM_005123 1.1 1.1 3.7 AK021798 AK021798 1.0 1.5 3.7 WFDC5 NM_145652 1.1 1.1 3.7 THC2540410 THC2540410 1.1 1.5 3.7 C3orf64 NM_173654 0.8 0.9 3.7 TMEM35 NM_021637 0.7 1.5 3.7 ANGPT1 NM_001146 1.1 1.1 3.7 CCDC65 NM_033124 1.1 1.5 3.7 SYCP2 NM_014258 1.1 1.1 3.7 THC2654991 THC2654991 1.1 1.1 3.7 GPR126 NM_198569 1.1 1.4 3.7 TMPRSS12 NM_182559 1.1 1.1 3.7 AK022645 AK022645 1.1 1.1 3.6 TITF1 NM_003317 1.1 1.1 3.6 AK093927 AK093927 1.1 1.1 3.6 C1orf210 NM_182517 1.1 1.1 3.6 FOXD1 NM_004472 1.1 1.1 3.6 ENST00000358356 ENST00000358356 0.8 1.4 3.6 BC030685 BC030685 1.1 1.1 3.6 GREM2 NM_022469 1.1 1.5 3.6 LMCD1 NM_014583 1.1 1.1 3.6 SLFN11 NM_152270 0.8 0.9 3.6 AK090480 AK090480 1.1 1.3 3.6 AW467174 AW467174 0.9 1.4 3.6 AK3L2 NM_001002921 1.1 1.5 3.6 A_24_P474384 A_24_P474384 1.1 1.1 3.6 RHOV ENST00000220507 0.8 1.7 3.6 MOV10L1 NM_018995 1.1 1.1 3.6 KRT18P41 XR_016695 0.8 1.7 3.6 MGC45438 NM_152459 1.1 1.1 3.6 PURG NM_001015508 1.1 1.1 3.6 BC031939 BC031939 1.1 1.1 3.6 NOPE NM_020962 1.2 1.0 3.6 THC2698352 THC2698352 1.1 1.3 3.6 ARHGAP6 NM_001174 1.1 1.3 3.6 LIPG NM_006033 1.1 1.1 3.6 AW978845 AW978845 1.1 1.1 3.6 LILRA5 NM_181879 1.1 1.1 3.5 ABCC9 NM_020297 1.1 1.1 3.5 ENST00000166133 ENST00000166133 0.7 1.3 3.5 ARHGEF4 NM_032995 1.1 1.1 3.5 OR4S1 NM_001004725 1.1 1.1 3.5 A_23_P395705 A_23_P395705 1.1 1.1 3.5 GZMK NM_002104 1.1 1.1 3.5 C3orf50 BC011266 1.1 1.3 3.5 MERTK U08023 1.1 1.1 3.5 AK054684 AK054684 1.1 1.1 3.5 CDS1 NM_001263 0.9 1.7 3.5 ENST00000317596 ENST00000317596 1.1 1.1 3.5 ANGPT2 NM_001147 1.1 1.1 3.5 HOXB5 NM_002147 1.1 1.1 3.5 THC2656116 THC2656116 1.1 1.1 3.5 KCNJ9 ENST00000368088 1.1 1.1 3.5 BG719660 BG719660 1.1 1.1 3.5 CB154245 CB154245 0.7 0.7 3.5 LOC388503 NM_001013640 1.1 1.1 3.5 PLA2G3 NM_015715 0.8 1.8 3.5 AK026881 AK026881 0.8 1.5 3.5 THC2705989 THC2705989 1.1 1.1 3.5 MIER2 AB033019 1.1 1.1 3.5 AK002066 AK002066 1.2 1.3 3.5 TGFBI NM_000358 1.1 1.2 3.5 ABCC11 NM_033151 1.1 1.1 3.4 HMGCS2 NM_005518 1.1 1.1 3.4 THC2516687 THC2516687 1.1 1.1 3.4 KIF19 NM_153209 1.1 1.1 3.4 BAPX1 NM_001189 1.1 1.2 3.4 BG547557 BG547557 1.1 1.1 3.4 KLRG2 ENST00000340940 0.8 1.6 3.4 BC029927 BC029927 1.1 1.1 3.4 BU629094 BU629094 1.3 1.1 3.4 TCEAL7 NM_152278 1.1 1.2 3.4 RPRM NM_019845 1.1 1.1 3.4 SNED1 NM_001080437 1.0 1.0 3.4 LOC729356 XR_015521 1.1 1.1 3.4 LOC401052 NM_001008737 1.1 1.1 3.4 AK023572 AK023572 1.1 1.1 3.4 PRDM9 NM_020227 1.1 1.1 3.4 BI758260 BI758260 1.1 1.1 3.3 THC2780391 THC2780391 0.9 1.6 3.3 PKD1L2 NM_052892 1.1 1.1 3.3 SLC40A1 NM_014585 1.1 1.1 3.3 ENST00000366822 ENST00000366822 1.1 1.1 3.3 ZCCHC2 ENST00000269499 1.1 1.1 3.3 BCAR4 CR606007 1.1 1.1 3.3 LEMD1 NM_001001552 1.1 1.1 3.3 THC2689572 THC2689572 0.7 1.3 3.3 A_24_P933410 A_24_P933410 1.1 1.1 3.3 BC015129 BC015129 1.1 0.9 3.3 GLUL NM_002065 1.1 1.1 3.3 LOC388610 NM_001013642 0.7 1.2 3.3 THC2657647 THC2657647 1.1 1.1 3.3 RAB3C NM_138453 1.1 1.1 3.3 ANKRD22 NM_144590 1.1 1.1 3.3 BU930695 BU930695 1.1 1.1 3.3 PAPSS2 NM_001015880 0.7 0.7 3.3 SAA3P AY209188 1.1 1.1 3.3 THC2529452 THC2529452 0.6 1.3 3.3 DNM3 NM_015569 0.8 1.6 3.3 LOC151146 AK021716 1.1 1.1 3.3 KCNE1 NM_000219 1.1 1.1 3.3 AA729924 AA729924 1.1 1.1 3.3 CHRNB4 NM_000750 1.1 1.1 3.2 CFTR NM_000492 0.7 1.4 3.2 C22orf24 AL050256 1.1 1.1 3.2 SRD5A2 NM_000348 1.0 1.2 3.2 LOC541473 NM_001013748 1.1 1.1 3.2 ENST00000315302 ENST00000315302 0.6 1.1 3.2 FLJ13236 NM_024902 1.1 1.0 3.2 BC024651 BC024651 1.0 1.2 3.2 GPR161 NM_153832 1.0 1.0 3.2 PRL NM_000948 0.8 0.7 3.2 AF086125 AF086125 0.7 1.4 3.2 THC2533951 THC2533951 0.8 1.3 3.1 LOC89944 NM_138342 1.0 0.6 3.1 HOXA4 NM_002141 0.7 1.0 3.0 A_23_P159163 A_23_P159163 0.8 0.8 3.0 A_24_P940385 A_24_P940385 0.7 1.3 3.0 MAGED4 NM_030801 0.8 1.3 3.0 ARHGAP20 NM_020809 0.7 1.0 2.9 A_32_P124392 A_32_P124392 0.9 0.9 2.9 AK001062 AK001062 0.7 1.3 2.9 CXCL12 NM_199168 0.9 0.9 2.8 CR597597 CR597597 0.8 1.0 2.8 C1orf115 NM_024709 0.7 0.7 2.8 GJA4 NM_002060 0.8 0.7 2.7 GCH1 NM_000161 0.6 1.1 2.6 DUSP13 NM_001007271 0.9 0.7 2.6 CR622072 CR622072 0.6 1.0 2.5 COL13A1 NM_005203 0.7 0.6 2.5 ROR2 NM_004560 0.8 0.7 2.5