Supplemental file 1: The whole list of tumor aberrations by time

tumor biopsy ctDNA

2002 (T1) 2012 (M1) 2015 (M2) 08/2015 09/2015 11/2015 02/2016 05/2016 07/2016 11/2016 02/2017 05/2017 07/2017 11/2017

PIK3CA Q546R PIK3CA Q546R PIK3CA Q546R PIK3CA Q546R 0.30% PIK3CA Q546R 1.30% PIK3CA Q546R 5.40% PIK3CA Q546R 12.50% PIK3CA Q546R 9.50% PIK3CA Q546R 32.58% PIK3CA Q546R 44.30% PIK3CA Q546R 15.40% PIK3CA Q546R 41.00%

TP53 E180K TP53 E180K TP53 E180K TP53 E180K 0.30% TP53 E180K 1.00% TP53 E180K 4.80% PIK3CA M1043I 0.20% PIK3CA M1043I 0.70% PIK3CA E453K 0.69% PIK3CA E453K 3.20% PIK3CA E453K 0.55% PIK3CA M1043I 0.20%

PIK3R2 S688* PIK3R2 S688* ATR E2579K VHL E173Q 0.40% PTEN Q245* 0.20% PTEN Q245* 0.30% PIK3CA E726K 1.50% PIK3CA E245Q 0.10% PIK3CA M1043I 0.36% PIK3CA M1043I 1.20% TP53 E180K 11.80% PIK3CA E453K 0.25%

PLCG2 P737T PLCG2 P737T PIK3CA E726K VHL E173Q 1.10% RB1 R556* 3.10% TP53 E180K 11.00% PIK3CA E726K 0.20% PIK3CA E726K 0.23% PIK3CA E726K 0.44% TP53 I195F 1.20% PIK3CA E39Q 0.53%

CDKN1B Q163* PIK3CA M1004I MET S1061F MET L229F 0.30% CCND1 E9K 0.10% PTEN Q245* 0.80% TP53 E180K 7.30% TP53 E180K 24.28% TP53 E180K 35.40% TP53 L137Q 1.30% TP53 E180K 38.40%

ERBB2 R487W PTEN S229* TBX3 S435* MET W112C 1.20% NF1 D1556N 1.30% TP53 I195F 0.20% TP53 R175G 0.20% TP53 I195F 1.70% ESR1 E380Q 7.10% TP53 I195F 0.56%

ALK E1407K RB1 Q217* SPEN Q743* NF1 R1176T 1.00% NF1 E76K 0.30% ESR1 E380Q 0.90% TP53 I195F 1.37% TP53 L137Q 2.10% ESR1 L391V 0.41% TP53 I254M 0.25%

APC E2637K PIK3CA D1017N PTEN I253M VHL E173Q 1.20% RB1 R556* 7.20% NF1 R1176T 0.50% TP53 I254S 0.12% ESR1 E380Q 7.70% TP53 R175G 0.12% TP53 L137Q 0.89%

ARID1B G2144E NF1 E924K APC F2762L 0.20% MET W112C 0.10% NF1 D1556N 0.30% TP53 L137Q 1.43% ESR1 L391V 0.51% PTEN D252N 0.37% ESR1 E380Q 28.30%

PTCH1 D599H SRC I429M AR R832P 0.20% AR R832P 0.50% APC E633K 0.20% ESR1 E380Q 2.44% ESR1 M357I 0.20% PTEN K66N 1.30% ESR1 L391V 0.27%

ERBB4 D335N EGFR M952I 1.30% EGFR M952I 2.40% AR R832P 0.60% NF1 Q2531* 8.16% PTEN D252N 1.01% NF1 R1176T 0.59% PTEN D252N 0.36%

BARD1 R664K MET L229F 3.90% APC E633K 0.40% PTEN Q245* 0.30% NF1 R1176T 7.00% PTEN K128N 0.18% NF1 Q2531* 1.20% PTEN K66N 1.50% Promoter PIK3CG G725S KIT S464L 1.10% APC F2762L 0.30% TERT –122C>T 0.40% PTEN K66N 2.14% PTEN K66N 7.40% FGFR1 K656E 1.40% NF1 Q2531* 0.88%

LRP1B E1467Q NOTCH1 S2341F 1.00% PTPN11 Q57E 2.10% EGFR M952I 1.10% EGFR M952I 9.16% PTEN L25F 0.36% EGFR M952I 1.34% NF1 S1150* 0.26%

RB1 R556* MYC G175S 0.50% VHL E173Q 3.30% FGFR3 S249C 0.10% MET W112C 7.50% PTEN Q171H 0.30% MET W112C 0.61% NF1 R1176T 0.89%

MLL K2855N NF1 E2558K 1.50% MET W112C 0.40% PTPN11 Q57E 0.38% NF1 Q2531* 1.80% FOXL2 E118Q 0.20% NF1 L552V 0.19%

PIK3C2B D791H APC M526I 0.30% PTPN11 Q57E 0.30% MTOR K1465N 13.05% NF1 D1556N 0.32% BRCA2 E2846K 0.28% FGFR1 K656E 1.80%

FAT1 D2913N PTEN P190L 0.20% RB1 R556* 3.40% MTOR R2505Q 0.57% NF1 R1176T 1.70% ERBB2 E1021K 0.26% EGFR M952I 1.19%

MET L229F KIT S464L 2.00% VHL E173Q 0.70% NPM1 D172N 4.57% NF1 E924K 0.27% CDKN2A F5L 0.55% ERBB2 E405K 0.27% Promoter RAF1 L613V NOTCH1 S2341F 2.40% CDKN2A F5L 0.10% MET L229F 22.52% TERT –122C>T 0.45% MET L229F 6.30% MET W112C 0.70%

HSP90AA1 L342V NOTCH1 L2067M 1.00% KIT S464L 1.10% ESR1 G442R 0.41% CCND1 S111C 0.25% NF1 E2558K 0.73% GNA11 E191K 0.18%

NSD1 K717N BRCA1 S616F 0.40% MET L229F 5.70% NF1 E2558K 6.77% MET W112C 2.16% FOXL2 H293Y 0.29% BRCA2 E2846K 0.22%

TET2 E330Q NTRK1 V341M 0.40% MYC G175S 0.70% FOXL2 H293Y 0.43% BRCA2 E2846K 0.57% NPM1 D172N 0.48% MET L229F 7.40%

CSF1R V406I CDKN2A F5L 0.20% NF1 E2558K 1.10% EGFR M952I 3.01% MTOR K1465N 4.17% NF1 E2558K 0.89%

PIK3C2B E807Q ARID1A L1029F 0.20% NOTCH1 S2341F 1.10% FGFR1 K656E 0.55% EGFR M636L 0.15%

RAD50 Q966E MET L229F 9.40% NOTCH1 L2067M 0.50% ERBB2 E1021K 0.71% MTOR K1465N 4.47%

MCL1 R80W NTRK1 V341M 0.30% FOXL2 E118Q 0.26% NPM1 D172N 0.38%

RANBP2 K997N MTOR K1465N 3.40% PTPN11 Q57E 0.34% CDK6 L33F 0.91%

FAT1 V912I MTOR K1465N 19.14% CDKN2A F5L 2.76%

NOTCH2 L2048H CDK4 I51M 0.21% BRCA1 E1527Q 0.13%

PRKDC S503C CDK6 L33F 0.19% VEGFA G39A 0.44%

MTOR K1465N CDKN2A F5L 0.80% KIT D439H 0.36%

FGFR2 I217M 0.20% MDM2 E273Q 0.16%

FOXL2 H293Y 1.54% GNAQ T175M 0.46%

MET L229F 28.40% ESR1 L469V 0.15%

NF1 E2558K 2.04%

NPM1 D172N 1.08%

PDGFRB A789T 0.21%

PTEN P190L 0.53%

SMO R726* 0.33%

Supplemental file 1: The whole list of tumor aberrations. Driver and predicted drivers by Cancer Genome Interpreter (CGI) are shaded in green. Sample T1 and M1 are sequenced and analyzed in Avera with results filtered by driver status. Sample M2 is tested with FoundationOne with a 315 gene panel. Liquid biopsies from 2015 to 2016 are sequenced with Guardent360 with a 70 gene panel. liquid biopsies from 2017 are sequenced with FoudationAct with a 67 gene panel. Supplemental File 2: Detailed information of driver and predicted driver mutations

Genomic coordinates Gene (GRCh37) HGVS cDNA HGVS protein Variant type dbSNP/COSMIC GenotypeID NM_004304: ALK chr2:29416734 c.4219G>A p.E1407K missense COSM7126334 heterozygous NM_000038: APC chr5:112179254 c.7909G>A p.E2637K missense . heterozygous NM_000038: APC chr5:112179575 c.8286C>A p.F2762L missense . heterozygous NM_000038: APC chr5:112170801 c.1897G>A p.E633K missense . heterozygous NM_000044: AR chrX:66942714 c.2495G>C p.R832P missense . heterozygous NM_017519: ARID1B chr6:157528745 c.6431G>A p.G2144E missense . heterozygous NM_001184: ATR chr3:142171996 c.7735G>A p.E2579K missense . heterozygous NM_000465: BARD1 chr2:215595145 c.1991G>A p.R664K missense rs1574706698 heterozygous NM_000059: BRCA2 chr13:32945141 c.8536G>A p.E2846K missense . heterozygous NM_053056: CCND1 chr11:69456106 c.25G>A p.E9K missense COSM6975262 heterozygous NM_053056： CCND1 chr11:69457932 c.332C>G p.S111C missense . heterozygous NM_004064: CDKN1B chr12:12871770 c.487C>T p.Q163* nonsense . heterozygous NM_005228: EGFR chr7:55268016 c.2856G>A p.M952I missense . heterozygous NM_004448: ERBB2 chr17:37872138 c.1459C>T p.R487W missense rs375382055 heterozygous NM_004448: ERBB2 chr17:37883158 c.3061G>A p.E1021K missense . heterozygous NM_004448: ERBB2 chr17:37871603 c.1213G>A p.E405K missense . heterozygous NM_005235: ERBB4 chr2:212576896 c.1003G>A p.D335N missense . heterozygous NM_000125: ESR1 chr6:152332832 c.1138G>C p.E380Q missense COSM3829320 heterozygous NM_000125: ESR1 chr6:152332865 c.1171C>G p.L391V missense . heterozygous NM_000125: ESR1 chr6:152265618 c.1071G>C p.M357I missense . heterozygous NM_005245: FAT1 chr4:187539003 c.8737G>A p.D2913N missense rs752221845 heterozygous NM_023110: FGFR1 chr8:38272308 c.1966A>G p.K656E missense rs869320694 heterozygous NM_000142: FGFR3 chr4:1803568 c.746C>G p.S249C missense rs121913483 heterozygous NM_023067: FOXL2 chr3:138665213 c.352G>C p.E118Q missense . heterozygous NM_002067: GNA11 chr19:3115036 c.571G>A p.E191K missense rs1317391449 heterozygous NM_018557: LRP1B chr2:141625339 c.4399G>C p.E1467Q missense . heterozygous NM_000245: MET chr7:116415034 c.3128C>T p.S1061F missense . heterozygous NM_000245: MET chr7:116339474 c.336G>C p.W112C missense . heterozygous NM_005933: MLL chr11:118375181c,8565G>C p.K2855N missense . heterozygous NM_001042492: NF1 chr17:29556403 c.2770G>A p.E924K missense . heterozygous NM_001042492: NF1 chr17:29559852 c.3449C>G p.S1150* nonsense rs1555614972 heterozygous NM_001042492: NF1 chr17:29679408 c.7591C>T p.Q2531* nonsense rs1555536372 heterozygous NM_001042492: NF1 chr17:29560050 c.3527G>C p.R1176T missense . heterozygous NM_001042492: NF1 chr17:29588817 c.4666G>A p.D1556N missense . heterozygous NM_001042492: NF1 chr17:29486049 c.226G>A p.E76K missense . heterozygous NM_001042492: NF1 chr17:29548880 c.1654C>G p.L552V missense . heterozygous NM_002646： PIK3C2B chr1:204416682 c.2371G>C p.D791H missense . heterozygous NM_006218: PIK3CA chr3:178928079 c.1357G>A p.E453K missense rs1057519925 heterozygous NM_006218: PIK3CA chr3:178936095 c.1637A>G p.Q546R missense rs397517201 heterozygous NM_006218: PIK3CA chr3:178938934 c.2176G>A p.E726K missense rs867262025 heterozygous NM_006218: PIK3CA chr3:178952074 c.3129G>A p.M1043I missense rs121913283 heterozygous NM_006218: PIK3CA chr3:178951957 c.3012G>A p.M1004I missense COSM1420933 heterozygous NM_006218: PIK3CA chr3:178951994 c.3049G>A p.D1017N missense . heterozygous NM_006218: PIK3CA chr3:178919248 c.733G>C p.E245Q missense . heterozygous NM_006218: PIK3CA chr3:178916728 c.115G>C p.E39Q missense . heterozygous NM_002649: PIK3CG chr7:106513269 c.2173G>A p.G725S missense COSM5609846 heterozygous NM_005027: PIK3R2 chr19:18279980 c.2063C>A p.S688* nonsense . heterozygous NM_002661: PLCG2 chr16:81953243 c.2209C>A p.P737T missense . heterozygous NM_001083603: PTCH1 chr9:98232147 c.1795G>C p.D599H missense . heterozygous NM_000314: PTEN chr10:89717661 c.686C>A p.S229* nonsense COSM6955728 heterozygous NM_000314: PTEN chr10:89717734 c.759C>G p.I253M missense . heterozygous NM_000314: PTEN chr10:89717708 c.733C>T p.Q245* nonsense rs786202918 heterozygous NM_000314: PTEN chr10:89685303 c.198G>C p.K66N missense . heterozygous NM_000314: PTEN chr10:89717729 c.754G>A p.D252N missense . heterozygous NM_000314: PTEN chr10:89692900 c.384G>C p.K128N missense rs1114167645 heterozygous NM_000314: PTEN chr10:89624301 c.75G>C p.L25F missense COSM39165 heterozygous NM_000314: PTEN chr10:89711895 c.513G>C p.Q171H missense COSM5179 heterozygous NM_002834: PTPN11 chr12:112888153c.169C>G p.Q57E missense . heterozygous NM_000321: RB1 chr13:48955550 c.1666C>T p.R556* nonsense rs121913304 heterozygous NM_000321: RB1 chr13:48934194 c.649C>T p.Q217* nonsense COSM13405 heterozygous NM_015001: SPEN chr1:16254962 c.2227C>T p.Q743* nonsense COSM6972141 heterozygous NM_005417: SRC chr20:36031168 c.1287C>G p.I429M missense . heterozygous NM_016569: TBX3 chr12:115112436c.1304C>G p.S435* nonsense COSM6531677 heterozygous NM_198253: p.promoter -124 TERT chr5:1295228 c.-124C>T C>T promoter rs1242535815 heterozygous NM_000546: TP53 chr17:7578392 c.538G>A p.E180K missense rs879253911 heterozygous NM_000546: TP53 chr17:7578407 c.523C>G p.R175G missense rs138729528 heterozygous NM_000546: TP53 chr17:7578266 c.583A>T p.I195F missense rs942158624 heterozygous NM_000546: TP53 chr17:7577520 c.761T>G p.I254S missense rs1330865474 heterozygous NM_000546: TP53 chr17:7578520 c.410T>A p.L137Q missense COSM44745 heterozygous NM_000546: TP53 chr17:7577519 c.762C>G p.I254M missense . heterozygous NM_000551: VHL chr3:10191524 c.517G>C p.E173Q missense COSM5037774 heterozygous Supplemental File 3: Clonal status of driver mutations in solid tumor samples

2002 (T1) 2012 (M1) 2015 (M2) Driver mutation Clonal status Driver mutation Clonal status Driver mutation Clonal status PIK3CA Q546R clonal PIK3CA Q546R clonal PIK3CA Q546R clonal TP53 E180K subclonal TP53 E180K clonal TP53 E180K clonal PLCG2 P737T subclonal PIK3CA M1004I clonal PTEN I253M clonal PIK3R2 S688* subclonal PIK3CA D1017N clonal NF1 E924K clonal CDKN1B Q163* subclonal ARID1B G2144E clonal SRC I429M clonal ERBB2 R487W subclonal PTCH1 D599H clonal TBX3 S435* clonal ALK E1407K subclonal PTEN S229* clonal SPEN Q743* clonal APC E2637K subclonal RB1 Q217* clonal ATR E2579K subclonal PLCG2 P737T subclonal PIK3CA E726K subclonal PIK3R2 S688* subclonal MET S1061F subclonal ERBB4 D335N subclonal BARD1 R664K subclonal PIK3CG G725S subclonal LRP1B E1467Q subclonal Supplemental File 4: Differentially expressed genes in T1 and M1

Up-regulated Genes Down-regulated Genes Gene Symbol EntrezID log2FC FDR Gene Symbol EntrezID log2FC FDR SPACA5B 729201 9.45 4.34E-25 FAM27A 100132948 -7.73 1.99E-35 SOX2 6657 7.60 4.34E-25 NKAIN1 79570 -7.18 9.30E-32 PTHLH 5744 7.33 6.96E-24 RBM24 221662 -6.57 1.09E-28 C7orf55-LUC7L2 100996928 6.98 1.18E-19 NPY1R 4886 -6.40 1.39E-27 OR52N2 390077 6.79 1.59E-19 TFF1 7031 -6.37 2.08E-27 PIK3C2G 5288 6.66 7.02E-19 STH 246744 -6.24 9.78E-24 WDR49 151790 6.56 3.91E-18 PEG10 23089 -6.18 8.37E-26 SENP3-EIF4A1 100533955 6.49 2.20E-16 SLC5A8 160728 -6.17 9.47E-26 SHISAL2B 100132916 6.43 4.07E-16 NECAB1 64168 -6.14 1.62E-25 EYA1 2138 6.24 3.56E-16 PPIAL4B 65350 -6.07 1.51E-23 CXCL17 284340 6.14 2.08E-15 FAM156B 727866 -6.06 1.63E-24 CCL3L3 414062 6.04 8.55E-14 PGR 5241 -6.05 6.48E-25 SERPINI2 5276 6.02 1.14E-14 ADCY1 107 -5.82 2.13E-23 CLGN 1047 5.71 6.08E-13 GREB1 9687 -5.72 1.53E-22 CCDC160 347475 5.65 1.74E-12 GFRA1 2674 -5.65 7.67E-22 ARL2-SNX15 100528018 5.55 4.70E-11 GRIA1 2890 -5.64 8.01E-22 OR52E4 390081 5.52 9.05E-12 CDC42EP2 10435 -5.61 3.46E-20 CEACAM5 1048 5.50 8.72E-12 GSTM5 2949 -5.54 4.74E-21 PPFIA2 8499 5.43 2.13E-11 CALML3 810 -5.36 2.09E-18 OR52N5 390075 5.32 2.22E-10 TMEM64 169200 -5.35 8.89E-20 RIMBP2 23504 5.26 1.78E-10 ELOVL2 54898 -5.33 1.45E-19 TP53TG3E 102724101 5.25 1.71E-09 SYTL5 94122 -5.16 2.22E-18 SLC44A5 204962 5.06 1.86E-09 MAPT 4137 -5.12 3.94E-18 APOC4-APOC2 100533990 5.00 2.26E-08 IGSF1 3547 -5.10 4.62E-18 LUZP6 767558 4.98 5.23E-08 GPR42 2866 -5.09 1.27E-16 BHLHE41 79365 4.98 3.64E-09 GRPR 2925 -5.08 5.61E-18 GP2 2813 4.97 4.12E-09 CACNG4 27092 -5.07 7.71E-18 USP17L21 100287478 4.91 5.43E-08 SCGB2A2 4250 -5.04 2.67E-17 OR52N4 390072 4.89 1.15E-08 MEGF10 84466 -4.96 3.91E-17 EEF1AKMT4-ECE2110599583 4.86 9.65E-08 ZDHHC22 283576 -4.91 2.66E-16 SCN11A 11280 4.82 2.23E-08 CYP24A1 1591 -4.89 1.52E-16 NPY4R 5540 4.70 4.30E-07 BEX1 55859 -4.89 1.55E-16 MTRNR2L6 100463482 4.68 8.15E-08 AGTR1 185 -4.88 1.85E-16 IGLV4-69 28784 4.68 1.03E-07 USP17L19 100287404 -4.75 1.02E-14 UTP14C 9724 4.64 6.37E-07 IL20 50604 -4.69 3.12E-15 PLEKHS1 79949 4.63 1.53E-07 VSTM2A 222008 -4.65 4.86E-15 PDE4D 5144 4.62 1.59E-07 PCDH19 57526 -4.63 5.93E-15 PRKAA2 5563 4.62 1.76E-07 PPP2R2C 5522 -4.60 1.06E-14 OR6F1 343169 4.60 1.35E-06 RGS9BP 388531 -4.58 1.31E-13 OR56B1 387748 4.59 2.31E-07 DACH1 1602 -4.51 3.56E-14 USP17L10 100287144 4.57 1.69E-06 AREG 374 -4.50 3.48E-14 MUC16 94025 4.55 3.03E-07 KCNC2 3747 -4.47 5.18E-14 OR51I2 390064 4.43 1.70E-06 ERICH3 127254 -4.42 1.20E-13 IGHV3-49 28423 4.42 1.08E-06 ADORA1 134 -4.42 2.32E-13 IGLV3-16 28799 4.41 1.60E-06 NELL1 4745 -4.36 2.62E-13 ANKRD30B 374860 4.39 1.33E-06 TRH 7200 -4.35 1.58E-12 KCNMB2 10242 4.39 5.58E-06 TRIM9 114088 -4.27 8.91E-13 LRRC31 79782 4.34 2.00E-06 IGLV1-36 28826 -4.24 1.20E-12 ZNF385B 151126 4.29 3.51E-06 PTGES 9536 -4.24 1.40E-12 OR52N1 79473 4.26 4.85E-06 DTNA 1837 -4.22 1.29E-12 CFHR4 10877 4.23 5.49E-06 MTRNR2L11 100463489 -4.13 8.82E-12 CFAP73 387885 4.21 1.23E-05 PDZRN4 29951 -4.11 6.04E-12 SSX3 10214 4.20 6.72E-06 RIMS4 140730 -4.10 1.16E-11 CAPZA3 93661 4.19 1.39E-05 PPP1R3C 5507 -4.05 1.40E-11 IL1RAPL2 26280 4.16 1.12E-05 TPRG1 285386 -4.03 1.55E-11 ABCA13 154664 4.14 1.19E-05 DDIT4L 115265 -4.02 2.05E-11 IGLV2-23 28813 4.14 1.18E-05 RGS7 6000 -4.00 2.45E-11 CSMD1 64478 4.12 1.41E-05 DHRS2 10202 -3.98 3.39E-11 HBG1 3047 4.11 3.65E-05 STC2 8614 -3.96 3.49E-11 S100P 6286 4.08 2.16E-05 PTPRT 11122 -3.94 4.19E-11 PLCZ1 89869 4.07 1.95E-05 CST9 128822 -3.94 5.86E-11 CYP4X1 260293 4.06 2.26E-05 DMRTC1 63947 -3.91 4.26E-10 OR8D2 283160 4.05 3.96E-05 SYT1 6857 -3.91 6.35E-11 ATRNL1 26033 4.05 2.33E-05 MALRD1 340895 -3.87 1.11E-10 PAGE2 203569 4.04 2.88E-05 LINGO1 84894 -3.87 1.26E-10 ARMC3 219681 4.03 2.96E-05 KLK11 11012 -3.84 3.69E-10 OR13G1 441933 4.02 4.40E-05 NTRK3 4916 -3.83 1.57E-10 MKRN3 7681 4.01 3.89E-05 PPFIA4 8497 -3.77 3.67E-10 TMTC2 160335 3.99 3.73E-05 TRIM67 440730 -3.75 5.32E-10 TCIM 56892 3.99 4.02E-05 CITED4 163732 -3.75 1.07E-08 EHF 26298 3.98 4.13E-05 SCUBE2 57758 -3.73 5.18E-10 NWD1 284434 3.97 4.32E-05 CST5 1473 -3.66 2.08E-09 OR8G1 26494 3.96 8.13E-05 CITED1 4435 -3.65 5.17E-09 OR14A2 388761 3.96 7.70E-05 PNPLA3 80339 -3.64 1.73E-09 CNMD 11061 3.94 7.34E-05 IGHV2-26 28455 -3.63 1.88E-09 MAGED4 728239 3.91 1.12E-04 PPP1R9A 55607 -3.61 2.04E-09 IGHV3OR16-12 28304 3.86 1.45E-04 ITGA2 3673 -3.60 2.14E-09 TMC5 79838 3.82 1.30E-04 PGLYRP2 114770 -3.58 4.43E-09 OR51B2 79345 3.81 2.37E-04 EPS8L3 79574 -3.58 3.40E-09 UBQLN3 50613 3.79 2.14E-04 GSTM3 2947 -3.56 3.03E-09 GLYATL2 219970 3.78 2.03E-04 OLFM1 10439 -3.52 5.80E-09 OR8B3 390271 3.77 2.41E-04 KRT5 3852 -3.51 6.90E-09 OR51B6 390058 3.76 2.56E-04 MSMB 4477 -3.51 2.05E-08 OR52D1 390066 3.76 2.39E-04 PDZK1 5174 -3.49 7.79E-09 IGLV3-21 28796 3.75 2.39E-04 DCDC2 51473 -3.48 8.96E-09 OR52B6 340980 3.72 3.14E-04 PHGR1 644844 -3.47 1.09E-08 GRIN1 2902 3.70 3.12E-04 NRIP3 56675 -3.39 2.56E-08 IQCJ 654502 3.70 1.36E-03 PHF21B 112885 -3.39 3.01E-08 OR51B5 282763 3.70 6.03E-04 FCRLB 127943 -3.37 3.34E-08 OR51Q1 390061 3.69 4.29E-04 VIL1 7429 -3.36 3.07E-08 ADAMDEC1 27299 3.69 3.53E-04 ASCL1 429 -3.30 2.23E-07 IGKV2D-29 28882 3.69 3.56E-04 SDK2 54549 -3.29 6.64E-08 PLCH1 23007 3.69 3.96E-04 ADAMTS15 170689 -3.24 1.09E-07 SSX1 6756 3.67 4.49E-04 INSYN1 388135 -3.24 1.36E-07 SIM2 6493 3.64 5.83E-04 ARHGAP36 158763 -3.23 1.22E-07 CEACAM6 4680 3.63 5.45E-04 GRIK3 2899 -3.22 1.24E-07 GALNT3 2591 3.62 5.83E-04 IGF1R 3480 -3.19 1.42E-07 MARK1 4139 3.62 5.99E-04 CNTN4 152330 -3.18 1.83E-07 TEN1-CDK3 100529145 3.61 9.74E-04 RGS6 9628 -3.17 1.93E-07 RHBDL3 162494 3.61 7.00E-04 CAP2 10486 -3.15 2.66E-07 TRIM34 53840 3.60 7.14E-04 MAGED4B 81557 -3.15 2.63E-07 OR8B2 26595 3.59 7.88E-04 SPACA5 389852 -3.15 2.80E-07 LIMS3-LOC440895 100271835 3.58 1.86E-03 LONRF2 164832 -3.14 3.03E-07 MUC13 56667 3.57 9.33E-04 EPHA8 2046 -3.14 4.52E-07 ADAMTS20 80070 3.57 8.69E-04 ITPRID2 6744 -3.14 2.80E-07 SLC7A11 23657 3.53 1.19E-03 THEG 51298 -3.13 1.56E-06 LUZP2 338645 3.52 1.30E-03 TENT5B 115572 -3.12 4.43E-07 CHN2 1124 3.50 1.38E-03 KCND3 3752 -3.11 3.82E-07 IGHV3-23 28442 3.49 1.47E-03 KRT17 3872 -3.09 4.18E-07 C3orf67 200844 3.47 1.59E-03 NRCAM 4897 -3.08 4.52E-07 TRIM36 55521 3.47 1.62E-03 COX6C 1345 -3.07 4.81E-07 EXPH5 23086 3.45 1.90E-03 IL1RAPL1 11141 -3.07 4.70E-07 ACY3 91703 3.45 2.48E-03 SYT8 90019 -3.00 3.06E-06 UBD 10537 3.43 2.40E-03 USP17L3 645836 -3.00 3.06E-06 IGLV3-1 28809 3.42 2.27E-03 ATP6V1B1 525 -2.99 1.16E-06 EFHC2 80258 3.41 2.70E-03 SERPINA3 12 -2.98 1.24E-06 IGHV1-18 28468 3.40 2.72E-03 PPP1R1C 151242 -2.98 1.38E-06 OR8B8 26493 3.38 3.81E-03 DSEL 92126 -2.97 1.33E-06 SLITRK6 84189 3.37 3.39E-03 CACNA1B 774 -2.97 1.31E-06 DCAF12L2 340578 3.37 3.80E-03 TBC1D3B 414059 -2.96 1.50E-06 UPRT 139596 3.37 3.42E-03 ADRA2C 152 -2.96 1.63E-06 FGF12 2257 3.36 3.68E-03 MTCL1 23255 -2.95 1.50E-06 ATP2C2 9914 3.35 3.70E-03 EDN1 1906 -2.94 1.74E-06 NKX3-1 4824 3.33 7.24E-03 SLC6A4 6532 -2.93 2.12E-06 IL12A 3592 3.31 5.91E-03 CCND1 595 -2.93 1.73E-06 UBQLNL 143630 3.31 5.56E-03 OR6B3 150681 -2.91 1.16E-05 IGHJ4 28477 3.31 5.25E-03 KCNK15 60598 -2.88 3.71E-06 IGHV3-15 28448 3.30 5.32E-03 HOXD9 3235 -2.86 9.26E-06 C5orf49 134121 3.30 7.54E-03 HPN 3249 -2.85 4.10E-06 TNFSF10 8743 3.30 5.39E-03 IRX4 50805 -2.85 6.77E-06 OR51M1 390059 3.29 6.40E-03 GJA1 2697 -2.84 4.25E-06 FGF10 2255 3.29 6.07E-03 NXPH3 11248 -2.84 4.75E-06 PKP1 5317 3.28 5.99E-03 CTNND2 1501 -2.83 4.68E-06 IL7 3574 3.28 6.74E-03 NFASC 23114 -2.83 4.44E-06 PGAP1 80055 3.28 6.31E-03 ZNF185 7739 -2.83 4.43E-06 LRMDA 83938 3.26 7.03E-03 SLC52A3 113278 -2.82 4.92E-06 GPC4 2239 3.25 7.47E-03 MAGEB17 645864 -2.82 9.39E-06 IGHG2 3501 3.23 8.01E-03 RNF186 54546 -2.81 5.62E-05 SPTB 6710 3.23 8.10E-03 EVA1A 84141 -2.81 2.07E-05 TRAV16 28667 3.23 2.09E-02 USP17L13 100287238 -2.81 1.17E-05 IGKV2-30 28919 3.22 8.65E-03 MYBPH 4608 -2.81 6.62E-06 MAP1B 4131 3.21 9.13E-03 CPA6 57094 -2.78 8.36E-06 MLLT3 4300 3.21 9.23E-03 WDR72 256764 -2.76 8.97E-06 SCN8A 6334 3.20 9.28E-03 KRTAP5-9 3846 -2.75 1.16E-05 GALNT14 79623 3.20 1.04E-02 KRT14 3861 -2.73 1.14E-05 KLHDC7A 127707 3.19 1.14E-02 ARTN 9048 -2.72 3.14E-05 DAB1 1600 3.16 1.38E-02 COL20A1 57642 -2.72 1.53E-05 OR8G5 219865 3.16 1.46E-02 SLC39A8 64116 -2.72 1.19E-05 FOXD1 2297 3.16 1.39E-02 PTGER3 5733 -2.72 1.26E-05 IGHV4-4 28401 3.16 1.33E-02 WDR17 116966 -2.72 1.18E-05 AK5 26289 3.15 1.50E-02 DOK7 285489 -2.71 1.33E-05 CEACAM1 634 3.15 1.42E-02 RASD1 51655 -2.71 1.37E-05 ALOX15B 247 3.15 1.50E-02 FGF4 2249 -2.70 1.14E-04 IGHJ2 28481 3.14 3.70E-02 SPPL2C 162540 -2.70 3.21E-05 FGF23 8074 3.13 1.60E-02 C5AR2 27202 -2.69 1.43E-05 EPHA6 285220 3.13 1.70E-02 RAMP3 10268 -2.68 1.76E-05 HOXB6 3216 3.11 1.88E-02 CTSG 1511 -2.66 2.66E-05 IGHJ3 28479 3.10 1.98E-02 AMZ1 155185 -2.66 2.22E-05 IGKV3-11 28914 3.10 1.85E-02 FGFR4 2264 -2.66 2.51E-05 CAPN9 10753 3.10 1.88E-02 KIF12 113220 -2.64 2.31E-05 MAATS1 89876 3.09 1.97E-02 IGLV3-32 28787 -2.62 6.75E-05 IGHV3OR16-9 28307 3.08 2.36E-02 TH 7054 -2.61 3.61E-05 POF1B 79983 3.08 2.04E-02 CDSN 1041 -2.59 3.40E-05 EAF2 55840 3.08 2.08E-02 SCGB3A1 92304 -2.58 1.79E-04 IGSF21 84966 3.07 2.23E-02 HOXA9 3205 -2.58 1.33E-04 COMMD3-BMI1 100532731 3.07 2.08E-02 TSSK2 23617 -2.58 6.10E-05 IGKV1-33 28933 3.07 2.14E-02 GRP 2922 -2.58 5.63E-05 RANBP3L 202151 3.07 2.34E-02 TPSG1 25823 -2.57 5.50E-05 ASRGL1 80150 3.06 2.43E-02 ARPP21 10777 -2.56 4.25E-05 MUC4 4585 3.05 2.45E-02 HSPB8 26353 -2.56 3.97E-05 IGKV1D-33 28896 3.05 2.69E-02 PITPNM2 57605 -2.55 4.44E-05 FOXJ1 2302 3.04 2.78E-02 TUBB2B 347733 -2.54 5.02E-05 HES6 55502 3.04 3.04E-02 ASIC2 40 -2.54 7.49E-05 TEKT2 27285 3.03 2.93E-02 CHST8 64377 -2.53 8.47E-05 ADAM28 10863 3.03 2.91E-02 DCX 1641 -2.52 6.07E-05 IGHV3-48 28424 3.01 3.08E-02 RGS5 8490 -2.51 6.76E-05 HUNK 30811 3.01 3.29E-02 HR 55806 -2.51 6.76E-05 OR1C1 26188 3.01 3.94E-02 CA12 771 -2.50 7.23E-05 ASB9 140462 3.01 3.28E-02 OR9A4 130075 -2.50 9.73E-05 AKAP5 9495 3.01 3.25E-02 WNT11 7481 -2.49 1.40E-04 SMC1B 27127 3.01 3.24E-02 TMEM26 219623 -2.49 8.23E-05 TTC6 319089 3.00 3.30E-02 SEZ6L 23544 -2.49 8.66E-05 CNTLN 54875 3.00 3.35E-02 WFDC10B 280664 -2.49 1.54E-04 TSPAN1 10103 3.00 3.44E-02 CPLX3 594855 -2.49 1.02E-04 IGHV3OR16-13 100287372 2.99 3.68E-02 AMIGO3 386724 -2.48 8.90E-05 DMBX1 127343 2.99 4.62E-02 CALB2 794 -2.48 9.25E-05 HS6ST2 90161 2.97 4.68E-02 MYOG 4656 -2.47 1.25E-04 KCNG3 170850 2.96 4.29E-02 INSYN2 642938 -2.47 8.67E-05 AL050302.1 NA 2.94 4.59E-02 SERPINA6 866 -2.47 9.10E-05 TMPRSS2 7113 2.94 4.81E-02 HECTD2 143279 -2.47 8.43E-05 KLF5 688 2.93 4.85E-02 C8orf88 100127983 -2.46 1.09E-04 PLEKHH2 130271 2.93 4.81E-02 SFRP1 6422 -2.46 1.11E-04 IGLC2 3538 2.93 4.81E-02 STC1 6781 -2.45 1.01E-04 SUSD3 203328 -2.44 1.06E-04 MYOZ3 91977 -2.44 1.30E-04 SLC4A10 57282 -2.43 1.22E-04 MGAM 8972 -2.41 1.37E-04 PPEF2 5470 -2.40 1.56E-04 C19orf33 64073 -2.39 1.68E-04 TUBB3 10381 -2.39 1.75E-04 ID4 3400 -2.39 1.97E-04 SYT12 91683 -2.36 2.08E-04 CT62 196993 -2.34 2.47E-04 COL1A2 1278 -2.34 2.19E-04 CCDC85A 114800 -2.33 2.51E-04 PIEZO2 63895 -2.33 2.30E-04 NPY4R2 100996758 -2.32 6.00E-04 GLB1L2 89944 -2.32 2.70E-04 EGR3 1960 -2.31 2.52E-04 GPR139 124274 -2.27 4.16E-04 SHANK1 50944 -2.26 4.16E-04 FAM43B 163933 -2.26 9.10E-04 WFDC13 164237 -2.25 5.96E-04 FUT9 10690 -2.25 5.48E-04 MDFI 4188 -2.25 5.48E-04 TBX5 6910 -2.25 4.30E-04 PLXNA4 91584 -2.25 4.12E-04 BAHCC1 57597 -2.24 4.47E-04 C16orf74 404550 -2.24 5.56E-04 PRKAR2B 5577 -2.24 4.40E-04 VEPH1 79674 -2.24 4.51E-04 SGK2 10110 -2.24 4.78E-04 SLC8A2 6543 -2.24 5.69E-04 GABRP 2568 -2.24 4.47E-04 MMP11 4320 -2.23 4.70E-04 WISP2 8839 -2.23 4.80E-04 KRT19 3880 -2.23 4.57E-04 TRIM74 378108 -2.23 4.77E-04 LAMC2 3918 -2.22 5.02E-04 GAL3ST1 9514 -2.22 8.36E-04 ECM1 1893 -2.22 4.84E-04 TRPA1 8989 -2.22 4.79E-04 SLC2A14 144195 -2.21 5.35E-04 RNF112 7732 -2.21 7.93E-04 JAKMIP3 282973 -2.21 5.53E-04 CARTPT 9607 -2.21 5.04E-04 OSR1 130497 -2.20 7.57E-04 COL1A1 1277 -2.20 5.39E-04 KLK8 11202 -2.20 1.23E-03 MRPS30 10884 -2.20 5.35E-04 ANXA8L1 728113 -2.19 7.42E-04 CST4 1472 -2.18 7.24E-04 ADAM11 4185 -2.18 7.27E-04 DSCAM 1826 -2.18 6.54E-04 RNF128 79589 -2.18 6.32E-04 PGBD5 79605 -2.18 6.82E-04 MAT1A 4143 -2.17 7.12E-04 NOS1AP 9722 -2.17 6.64E-04 OPRPN 58503 -2.17 9.68E-04 MAPK8IP2 23542 -2.17 6.87E-04 SLC17A9 63910 -2.17 6.64E-04 MAG 4099 -2.17 7.65E-04 DNAJC12 56521 -2.16 7.41E-04 CA8 767 -2.14 8.76E-04 COL3A1 1281 -2.13 9.00E-04 RAB31 11031 -2.13 8.99E-04 WSCD2 9671 -2.13 1.04E-03 KNDC1 85442 -2.13 1.02E-03 KRT15 3866 -2.13 9.16E-04 NAT1 9 -2.12 9.60E-04 SPOCK1 6695 -2.12 9.48E-04 SOWAHC 65124 -2.11 1.08E-03 NEO1 4756 -2.11 1.01E-03 MSX2 4488 -2.11 1.13E-03 MYT1 4661 -2.11 1.04E-03 EMX1 2016 -2.11 1.12E-03 NCCRP1 342897 -2.10 1.33E-03 TSPAN5 10098 -2.10 1.06E-03 CLEC4G 339390 -2.10 1.92E-03 FAM236C 109729126 -2.10 1.92E-03 PRSS50 29122 -2.10 1.16E-03 ZNF703 80139 -2.10 1.04E-03 SLC22A31 146429 -2.09 2.68E-03 CD276 80381 -2.09 1.12E-03 FLT3 2322 -2.09 1.11E-03 NRSN1 140767 -2.09 1.10E-03 TMEM59L 25789 -2.08 1.51E-03 PREX1 57580 -2.07 1.22E-03 FOXN1 8456 -2.07 1.36E-03 IFITM10 402778 -2.07 1.21E-03 SFRP2 6423 -2.07 1.18E-03 THBS2 7058 -2.06 1.26E-03 NR6A1 2649 -2.06 1.37E-03 PMAIP1 5366 -2.06 1.33E-03 TTC39A 22996 -2.06 1.25E-03 CPZ 8532 -2.05 1.44E-03 HIST1H1A 3024 -2.05 1.94E-03 HOXD1 3231 -2.04 2.31E-03 PLPPR3 79948 -2.04 1.59E-03 PLS3 5358 -2.04 1.46E-03 GLIS1 148979 -2.04 2.38E-03 ANXA9 8416 -2.03 1.63E-03 ABAT 18 -2.03 1.56E-03 NRXN3 9369 -2.03 1.54E-03 PLPP4 196051 -2.03 1.73E-03 THRSP 7069 -2.02 2.12E-03 HMGCLL1 54511 -2.01 2.01E-03 IGLV9-49 28773 -2.01 2.01E-03 PON3 5446 -2.01 1.83E-03 MAOA 4128 -2.01 1.75E-03 C1orf226 400793 -2.01 1.76E-03 HOXD3 3232 -2.00 6.49E-03 AZU1 566 -2.00 2.63E-03 LEP 3952 -2.00 2.26E-03 TMPRSS6 164656 -2.00 1.90E-03 KRTAP10-2 386679 -1.98 2.78E-03 ASPG 374569 -1.98 2.48E-03 RAB40A 142684 -1.97 2.42E-03 MRGPRF 116535 -1.97 2.65E-03 IGFBP4 3487 -1.97 2.22E-03 NR5A1 2516 -1.96 2.78E-03 PODN 127435 -1.96 2.34E-03 TM6SF2 53345 -1.96 2.95E-03 DIRAS1 148252 -1.95 4.30E-03 CT45A7 101060211 -1.95 2.60E-03 CCDC170 80129 -1.95 2.43E-03 TMEM200B 399474 -1.95 3.96E-03 OR1E1 8387 -1.94 3.16E-03 VGF 7425 -1.93 5.49E-03 GRB14 2888 -1.93 2.95E-03 CHST1 8534 -1.93 2.78E-03 DGAT2 84649 -1.93 2.78E-03 SEMA3B 7869 -1.93 2.61E-03 BEND7 222389 -1.92 3.15E-03 FHOD3 80206 -1.92 2.94E-03 TCN1 6947 -1.92 2.95E-03 ELOA3D 100506888 -1.91 6.96E-03 SPATA18 132671 -1.91 3.19E-03 LGALS7 3963 -1.91 3.92E-03 S100A7 6278 -1.91 4.13E-03 PPM1J 333926 -1.90 3.44E-03 PDE5A 8654 -1.90 3.30E-03 TPSAB1 7177 -1.89 3.57E-03 RAPGEFL1 51195 -1.89 3.54E-03 TBX3 6926 -1.89 3.47E-03 GDF5 8200 -1.89 4.14E-03 TCEAL9 51186 -1.88 3.72E-03 FHL2 2274 -1.88 3.70E-03 NOVA1 4857 -1.88 3.64E-03 CSTL1 128817 -1.87 4.78E-03 CRIP3 401262 -1.86 4.65E-03 PPM1E 22843 -1.86 4.10E-03 CYP2B6 1555 -1.85 4.26E-03 KRTAP5-7 440050 -1.85 4.48E-03 TUB 7275 -1.84 4.72E-03 AP3B2 8120 -1.84 4.68E-03 KANK4 163782 -1.84 4.72E-03 FIBIN 387758 -1.84 4.84E-03 P2RX6 9127 -1.84 5.41E-03 CRABP1 1381 -1.84 5.43E-03 HAS1 3036 -1.84 5.43E-03 RAMP1 10267 -1.84 5.07E-03 ZDHHC11 79844 -1.84 4.44E-03 EFNB1 1947 -1.83 4.73E-03 ADRA2A 150 -1.83 4.91E-03 COL5A2 1290 -1.83 4.62E-03 TPSB2 64499 -1.83 4.72E-03 SDSL 113675 -1.82 5.08E-03 MYC 4609 -1.82 4.98E-03 PCK1 5105 -1.82 5.02E-03 NRIP1 8204 -1.82 4.86E-03 MAST4 375449 -1.82 4.83E-03 COL12A1 1303 -1.82 4.83E-03 SOX7 83595 -1.81 8.98E-03 IGFL1 374918 -1.81 8.18E-03 CRHR1 1394 -1.81 6.62E-03 KRT37 8688 -1.81 6.37E-03 MGP 4256 -1.81 5.14E-03 PKD1L2 114780 -1.81 5.10E-03 MYADM 91663 -1.81 5.06E-03 PARD6B 84612 -1.80 5.49E-03 NRG1 3084 -1.80 5.81E-03 NR2E3 10002 -1.80 5.56E-03 G0S2 50486 -1.79 6.74E-03 DBX1 120237 -1.79 8.11E-03 HRH3 11255 -1.79 8.11E-03 UBE2QL1 134111 -1.79 8.11E-03 KCNH1 3756 -1.79 5.90E-03 EGLN2 112398 -1.79 5.80E-03 RIC3 79608 -1.79 5.81E-03 MMP2 4313 -1.79 5.67E-03 SERPINA12 145264 -1.79 5.85E-03 COL13A1 1305 -1.78 6.65E-03 PENK 5179 -1.77 1.20E-02 IER5L 389792 -1.76 7.33E-03 B3GNT10 100288842 -1.76 8.83E-03 SEMA6D 80031 -1.76 6.91E-03 CPA3 1359 -1.75 7.36E-03 C1QTNF5 114902 -1.75 7.38E-03 NKX6-1 4825 -1.75 8.50E-03 MPPED2 744 -1.75 7.53E-03 BHLHE40 8553 -1.74 7.72E-03 CYP4F22 126410 -1.74 7.81E-03 HS3ST5 222537 -1.74 9.11E-03 GALNT5 11227 -1.74 7.79E-03 SEC14L2 23541 -1.74 7.49E-03 FAM189A2 9413 -1.74 7.51E-03 SUSD4 55061 -1.74 7.44E-03 CLDN14 23562 -1.73 9.60E-03 LRRC15 131578 -1.73 7.92E-03 SLC6A11 6538 -1.72 9.17E-03 NTNG1 22854 -1.72 8.82E-03 CEMP1 752014 -1.72 8.79E-03 HSPB1 3315 -1.72 8.20E-03 KRT80 144501 -1.72 8.28E-03 MYH1 4619 -1.72 8.23E-03 SMOC2 64094 -1.72 8.16E-03 COL6A1 1291 -1.71 8.73E-03 GAS1 2619 -1.70 9.29E-03 OPTC 26254 -1.70 9.07E-03 GRIK4 2900 -1.69 9.48E-03 CALCA 796 -1.69 1.24E-02 CELA3B 23436 -1.69 1.24E-02 FAM189A1 23359 -1.69 1.24E-02 DNAH10 196385 -1.68 1.00E-02 PTPRCAP 5790 -1.68 1.72E-02 PEX5L 51555 -1.68 1.03E-02 FRMPD1 22844 -1.68 1.01E-02 CPXM1 56265 -1.67 1.08E-02 CNPY1 285888 -1.67 1.42E-02 ECE2 9718 -1.67 1.30E-02 RPH3AL 9501 -1.66 1.21E-02 CCL26 10344 -1.66 1.71E-02 PLAT 5327 -1.65 1.21E-02 NT5DC3 51559 -1.65 1.19E-02 PXDN 7837 -1.65 1.16E-02 FAM180A 389558 -1.65 1.71E-02 SPARC 6678 -1.65 1.15E-02 HNRNPA1P48 642659 -1.65 1.16E-02 COL6A2 1292 -1.64 1.25E-02 KLK4 9622 -1.64 1.27E-02 DYRK3 8444 -1.64 1.22E-02 NTF3 4908 -1.64 1.26E-02 IGFN1 91156 -1.64 1.20E-02 MAS1L 116511 -1.63 1.67E-02 EDN3 1908 -1.63 1.39E-02 PCDH7 5099 -1.63 1.29E-02 SLC22A7 10864 -1.63 1.49E-02 SLC22A11 55867 -1.62 1.66E-02 RAET1L 154064 -1.62 1.51E-02 KRT16 3868 -1.62 1.38E-02 TNFRSF12A 51330 -1.62 1.46E-02 MMP3 4314 -1.62 1.38E-02 KCNQ3 3786 -1.62 1.35E-02 CXCR1 3577 -1.62 1.45E-02 ANO2 57101 -1.62 1.34E-02 KRT6B 3854 -1.62 1.33E-02 SORCS2 57537 -1.61 1.44E-02 KRT8 3856 -1.61 1.40E-02 NLRP5 126206 -1.61 1.46E-02 ELN 2006 -1.61 1.39E-02 GPR179 440435 -1.61 1.43E-02 COL5A1 1289 -1.61 1.38E-02 CTXN3 613212 -1.61 1.65E-02 GRIK5 2901 -1.60 1.55E-02 CTGF 1490 -1.60 1.50E-02 PI15 51050 -1.60 1.60E-02 LAMA3 3909 -1.60 1.48E-02 CYP4F11 57834 -1.60 1.48E-02 IGFBP5 3488 -1.60 1.47E-02 CACNA1H 8912 -1.60 1.45E-02 HECW2 57520 -1.59 1.56E-02 FBLN2 2199 -1.59 1.55E-02 GRIA2 2891 -1.59 1.56E-02 FAM169A 26049 -1.59 1.54E-02 PTN 5764 -1.59 1.59E-02 SIAH2 6478 -1.58 1.62E-02 FNDC1 84624 -1.58 1.60E-02 PDGFRL 5157 -1.58 1.61E-02 CELSR2 1952 -1.58 1.57E-02 LRRC38 126755 -1.58 3.17E-02 LYPD2 137797 -1.58 2.83E-02 SCGB1D2 10647 -1.58 2.63E-02 POU2F3 25833 -1.57 1.72E-02 NEFL 4747 -1.57 1.86E-02 NRN1 51299 -1.57 1.79E-02 NAV3 89795 -1.57 1.64E-02 TNXB 7148 -1.57 1.63E-02 COL22A1 169044 -1.57 1.66E-02 DACT3 147906 -1.57 1.72E-02 TNFAIP6 7130 -1.56 1.80E-02 SLC9A3R1 9368 -1.56 1.72E-02 RGS22 26166 -1.56 1.72E-02 ASXL3 80816 -1.56 1.71E-02 FTCDNL1 348751 -1.56 1.85E-02 IRX3 79191 -1.55 1.86E-02 TEX44 165100 -1.55 2.36E-02 LUM 4060 -1.55 1.84E-02 ORM1 5004 -1.55 1.92E-02 STON1-GTF2A1L286749 -1.55 1.84E-02 MYL9 10398 -1.55 1.78E-02 FCN2 2220 -1.55 1.93E-02 ADAMTS1 9510 -1.55 1.77E-02 RHOBTB1 9886 -1.54 1.98E-02 MFAP2 4237 -1.54 1.96E-02 NICN1 84276 -1.54 2.00E-02 KLF17 128209 -1.54 2.17E-02 ACTA1 58 -1.54 1.92E-02 SIGLEC15 284266 -1.53 2.25E-02 NPAS1 4861 -1.53 2.20E-02 PKDCC 91461 -1.53 2.10E-02 EVA1B 55194 -1.53 2.13E-02 SLC1A2 6506 -1.53 2.08E-02 CYP2S1 29785 -1.53 2.09E-02 PNLDC1 154197 -1.53 2.13E-02 CPE 1363 -1.53 2.02E-02 EMILIN1 11117 -1.53 2.01E-02 PRAMEF4 400735 -1.53 2.13E-02 MB21D2 151963 -1.52 2.23E-02 FOXI2 399823 -1.52 2.58E-02 PRSS37 136242 -1.52 2.19E-02 RAB6C 84084 -1.52 2.11E-02 RRAD 6236 -1.52 2.51E-02 LIM2 3982 -1.51 2.40E-02 ADGRA1 84435 -1.51 2.75E-02 NAT8L 339983 -1.51 2.75E-02 HHIPL1 84439 -1.51 2.35E-02 HAND2 9464 -1.51 2.56E-02 LGR6 59352 -1.51 2.23E-02 AMBP 259 -1.51 2.34E-02 IGDCC4 57722 -1.51 2.25E-02 CXXC5 51523 -1.51 2.19E-02 OTUD7A 161725 -1.50 2.38E-02 CDC20B 166979 -1.50 2.33E-02 KIAA1549L 25758 -1.50 2.33E-02 SP5 389058 -1.50 3.46E-02 ZFHX4 79776 -1.50 2.30E-02 NBL1 4681 -1.50 2.30E-02 Supplemental File 5: Differentially regulated pathways with intersection

Down-regulated pathways Pathway name KEGG ID p.value Intersection Protein digestion and absorption KEGG:04974 1.24E-05 ELN,COL1A1,COL12A1,SLC8A2,COL5A1,COL6A1,COL6A2,CPA3,COL1A2, COL3A1,COL22A1,COL13A1,COL5A2,CELA3B Neuroactive ligand-receptor interaction KEGG:04080 5.45E-03 PTGER3,GABRP,P2RX6,CTSG,HRH3,GRIK5,CRHR1,GRIA2,GRPR,AGTR1, GRIK4,ADRA2A,GRIA1,ADORA1,GRIK3,NPY1R,LEP,ADRA2C,NPY4R2 ECM-receptor interaction KEGG:04512 1.76E-02 LAMA3,LAMC2,COL1A1,COL6A1,COL6A2,ITGA2,COL1A2,TNXB,THBS2 PI3K-Akt signaling pathway KEGG:04151 3.15E-02 LAMA3,LAMC2,PPP2R2C,FGF4,SGK2,COL1A1,AREG,CCND1,FLT3,PCK1,MYC, IGF1R,COL6A1,COL6A2,FGFR4,ITGA2,COL1A2,TNXB,NTF3,THBS2 Estrogen signaling pathway KEGG:04915 3.58E-02 PGR,MMP2,KRT37,KRT17,TFF1,ADCY1,KRT19,KRT15,CALML3,KRT16,KRT14

Up-regulated pathways Pathway name KEGG ID p.value Intersection Olfactory transduction KEGG:04740 4.35E-12 OR51B5,OR51Q1,OR6F1,OR51B6,OR52E4,OR52N2,OR52N1,OR52N5,OR56B1, OR52N4,OR52D1,OR51M1,OR52B6,OR51I2,OR8B8,OR13G1,OR8G1,OR1C1, OR8G5,OR51B2,OR8D2,OR8B3,OR8B2