Supplementary Materials for

Identification of candidate biomarkers for Idiopathic Thrombocytopenic Purpura by Bioinformatics Analysis of Microarray Data

Samira Gilanchi, Hakimeh Zali*, Mohammad Faranoush*, Mostafa Rezaei Tavirani, Keyvan Shahriary and Mahyar Daskareh

To whom correspondence should be addressed. E-mail [email protected]; [email protected]

Volume 19, issue 4 (autumn 2020)

This PDF file includes:

Tables S1 to S8

Table S1. Up-regulated DEGs that obtain from analysis from 7 newly diagnosed ITP than 6 chronic ITP samples. In table M means log2FC, T is T statistics, P-values evaluated based on Benjamini false discovery rate. Top genes are selected for more valuation with P-value < 0.05, and B is B statistic.

Up-regulated genes M T P-Value B 1 FNBP4 1.089255 9.645201 0.0067318 6.692063 2 G2E3 0.993745 7.38905 0.0306136 4.269833 3 SAR1B 1.523974 7.35994 0.0306136 4.233735 4 PER3 1.297768 7.261088 0.0306136 4.11015 5 MSI2 1.60714 7.23665 0.0306136 4.079358 6 CASK 1.854101 7.07773 0.0324118 3.876782 7 TM2D1 1.510449 7.006354 0.0326833 3.784474 8 RPRD1A 1.155052 6.971092 0.0326833 3.738565 9 SLC39A6 1.032869 6.868857 0.033521 3.604313 10 CAMTA1 2.258868 6.855413 0.033521 3.586531 11 PTAR1 1.602835 6.828607 0.033521 3.550986 12 LOC101929734 1.620399 6.561583 0.039368 3.190433 13 ADNP2 1.084491 6.519255 0.0400375 3.132189 14 ZNF224 1.234505 6.365865 0.0400375 2.918603 15 TUBE1 0.990095 6.354317 0.0400375 2.902363 16 GIGYF2 0.741529 6.353043 0.0400375 2.900571 17 ABCA5 1.293839 6.341226 0.0400375 2.883927 18 FBXW7 1.205229 6.303732 0.0400375 2.830962 19 METTL8 1.073161 6.298249 0.0400375 2.823197 20 IL1RAP 1.257333 6.24383 0.0404726 2.74585 21 TNRC6A 0.894899 6.218077 0.0404726 2.709073 22 GSPT1 1.406084 6.210119 0.0404726 2.697685 23 FAM178A 1.428243 6.187739 0.0404726 2.665603 24 GFPT1 1.229498 6.155903 0.0404726 2.619821 25 BAZ1B 0.63851 6.098917 0.0416029 2.537444 26 IFNGR1 1.406398 6.044768 0.0435208 2.458658 27 TAOK1 1.135816 6.031329 0.0435546 2.439026 28 MIER3 1.470019 6.010599 0.0437901 2.408686 29 EML4 1.21403 5.992304 0.0437901 2.381849 30 SF1 2.419055 5.979368 0.0437901 2.36284 31 BBS2 0.900097 5.966395 0.0437901 2.343747 32 DYNC1LI2 0.94218 5.935166 0.0437901 2.29767 33 GPATCH11 0.768424 5.923691 0.0437901 2.280697 34 SCARB2 1.14523 5.922954 0.0437901 2.279606 35 PJA2 1.008988 5.910003 0.0439652 2.260422 36 RAB8B 1.803071 5.867977 0.0451902 2.197976 37 C2orf49 0.631136 5.839604 0.0451902 2.155649 38 CLIP1 1.182693 5.837234 0.0451902 2.152107 39 CAPN7 0.64129 5.816295 0.0451902 2.120774 40 TMED2 1.869119 5.805709 0.0451902 2.104904 41 TBC1D5 0.615565 5.779152 0.0451902 2.06501 42 ELL2 1.252154 5.731373 0.0451902 1.992939 43 ATF2 0.947451 5.711385 0.0451902 1.962674 44 GSPT1 0.873036 5.709465 0.0451902 1.959763 45 LINS 1.566022 5.699534 0.0451902 1.944699 46 SOCS5 1.382893 5.680112 0.0451902 1.915188 47 PAK2 0.922675 5.679562 0.0451902 1.914352 48 ERO1L 0.743072 5.664249 0.0451902 1.891038 49 ZNF382 1.33402 5.649846 0.0451902 1.869075 50 AKT3 1.097085 5.64984 0.0451902 1.869067 51 DNAJB14 1.2606 5.642786 0.0451902 1.858296 52 KIAA0430 0.830526 5.631546 0.0451902 1.841119 53 LOC283357 1.388744 5.614235 0.0451902 1.814622 54 ABL2 0.970876 5.611618 0.0451902 1.810612 55 EIF4E3 1.490178 5.581755 0.0461011 1.764772 56 FBXO38 1.473477 5.563832 0.0461011 1.737189 57 BUB3 0.846439 5.559647 0.0461011 1.730741 58 FOXN3 0.729011 5.551631 0.0461011 1.718382 59 FYCO1 0.685791 5.550846 0.0461011 1.71717 60 RCOR3 1.111475 5.540362 0.0461011 1.700989 61 CELF2 0.950587 5.514707 0.0461011 1.661313 62 LOC286161 0.874993 5.496367 0.0461011 1.632884 63 MID2 2.498842 5.487535 0.0461011 1.619173 64 VIM 1.077912 5.478964 0.0461011 1.605856 65 FKBP5 1.340329 5.462894 0.0461011 1.580853 66 DDI2 0.802653 5.447908 0.0461011 1.557498 67 FAM102B 1.604417 5.441605 0.0461011 1.547664 68 SSR1 0.671231 5.41403 0.0464563 1.504564 69 USP33 1.082804 5.413965 0.0464563 1.504464 70 LOC441155 1.320178 5.407527 0.0465531 1.494382 71 EBLN3 0.865344 5.399293 0.0465531 1.48148 72 TAOK1 1.238425 5.394765 0.0465619 1.47438 73 FEM1C 1.176922 5.381844 0.0468877 1.454102 74 PHLPP2 0.842615 5.377182 0.0468877 1.446778 75 KATNBL1 1.066378 5.369693 0.0468877 1.435007 76 RYK 1.038018 5.369199 0.0468877 1.434229 77 PCF11 0.923752 5.346921 0.0480425 1.399155 78 ZNF652 0.702938 5.320464 0.049098 1.357397

Table S2. Down-regulated DEGs that obtain from analysis from 7 newly diagnosed ITP and 6 chronic ITP samples. In table M means log2FC, T is T statistics, P-values evaluated based on Benjamini false discovery rate. Top genes are selected for more valuation with P-value < 0.05, and B is B statistics

Down- regulated genes M t P-Value B

1 ANPEP -0.735878826 -9.534773023 0.006731833 6.589335938

2 CHST2 -1.88015076 -8.319640697 0.017919754 5.355538925

3 DTX1 -1.749320818 -8.249838309 0.017919754 5.278554231

4 HDAC1 -0.774621454 -7.334693025 0.030613591 4.202317954

5 RNF123 -1.692692914 -7.289549357 0.030613591 4.145891021

6 AIF1 -1.004697039 -6.753471759 0.035415994 3.450729146

7 ATG7 -1.053550632 -6.721844599 0.035415994 3.408247991

8 FTH1P5 -0.626809793 -6.652339759 0.037015382 3.314307169

9 LOC100134317 -1.193919711 -6.629978435 0.037015382 3.283913481

10 SETMAR -0.837673399 -6.372754087 0.04003745 2.928280907

11 ACRC -0.923974318 -6.328993446 0.04003745 2.866672611

12 ZNF324 -1.293234841 -6.299714425 0.04003745 2.82527201

13 LOC100130093 -1.091433807 -6.237114887 0.04047256 2.736270886

14 DAGLB -1.12014016 -6.1993276 0.04047256 2.682226349

15 DUSP22 -0.69810855 -6.143905623 0.04047256 2.60252354

16 DAP -1.15484218 -6.110946593 0.041602909 2.554878573 17 KPNA2 -0.757591152 -5.96667344 0.043790091 2.34415709

18 TOPORS-AS1 -1.026182831 -5.927690522 0.043790091 2.286615563

19 SMIM12 -1.164931094 -5.8345256 0.045190183 2.148057695

20 ARRB1 -1.855926621 -5.831570925 0.045190183 2.143639442

21 TBC1D9B -1.003040692 -5.79978503 0.045190183 2.096015561

22 FARSA -1.089148521 -5.760964566 0.045190183 2.037621166

23 TUFM -0.737102234 -5.746319758 0.045190183 2.015526331

24 PPM1G -0.809004205 -5.698111162 0.045190183 1.942538785

25 MAU2 -0.725621444 -5.688755813 0.045190183 1.928329651

26 CYB561A3 -1.291094781 -5.68285354 0.045190183 1.919357586

27 MRPL45 -0.600284876 -5.671898012 0.045190183 1.902688575

28 TEX264 -0.96019039 -5.654495545 0.045190183 1.876169124

29 GRK5 -0.896145434 -5.654157813 0.045190183 1.875653956

30 COPRS -0.973549797 -5.52372126 0.046101091 1.675266232

31 MFNG -0.666183832 -5.49299702 0.046101091 1.627653526

32 HIST1H2BK -1.427762269 -5.488703475 0.046101091 1.620987469

33 TOPORS-AS1 -0.748894367 -5.486521934 0.046101091 1.617599291

34 TEX264 -0.971091862 -5.482213726 0.046101091 1.610905853

35 AIF1 -1.159172706 -5.481899391 0.046101091 1.610417367

36 PLA2G6 -0.971440161 -5.473211953 0.046101091 1.59691037

37 TBC1D13 -0.988326082 -5.471430671 0.046101091 1.59413934

38 COMMD9 -0.765036844 -5.469800785 0.046101091 1.59160337

39 RHOG -1.37279767 -5.467830565 0.046101091 1.588537282

40 TOX2 -1.727269695 -5.464495332 0.046101091 1.583345479

41 EIF4E2 -1.052136382 -5.460569655 0.046101091 1.577232208

42 MEN1 -1.034120822 -5.454648946 0.046101091 1.568007362

43 LASP1 -0.831433786 -5.446247014 0.046101091 1.554906698

44 TMEM214 -1.042821964 -5.429086581 0.046456312 1.528113287

45 UBE2R2 -0.859762728 -5.421047185 0.046456312 1.515544335

46 HDAC7 -0.861652419 -5.400374922 0.046553106 1.48317619

47 B4GALT7 -0.873618293 -5.3516994 0.047991908 1.406684887

48 PUSL1 -1.015661172 -5.339559454 0.048314234 1.387547283 49 ABHD16A -0.708618318 -5.32449758 0.049097958 1.363770168

50 CDIP1 -0.860815247 -5.318151293 0.049097958 1.353740696

51 UBAP2 -0.735560264 -5.31243509 0.049244602 1.344701393

52 TUBA1A -0.85617395 -5.305815959 0.04947288 1.334227626

53 UQCR11 -0.712583116 -5.30149897 0.049503945 1.327392822

Table S3. Gene ontology enrichment based on biological process term for up-regulated DEGs. They were selected with P-value < 0.05 as the significant biological process. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes

Annotation Cluster 1 Enrichment Score: 1.6089173346492356 DYNC1LI2, RAB8B, TAOK1, VIM, EML4, ATF2, BBS2, GO:1902589 single-organism organelle organization 0.005313 FBXW7, CLIP1, TUBE1, FYCO1, USP33, ABL2, BUB3

GO:0000226 microtubule cytoskeleton organization 0.020728 BBS2, DYNC1LI2, CLIP1, TUBE1, USP33, EML4 BBS2, DYNC1LI2, CLIP1, TUBE1, FYCO1, USP33, GO:0007017 microtubule-based process 0.026109 EML4

Annotation Cluster 2 Enrichment Score: 1.5454786370206883

GO:0010506 regulation of autophagy 0.003125 FBXW7, TBC1D5, ABL2, FYCO1, USP33, MID2

GO:0010508 positive regulation of autophagy 0.03688 TBC1D5, FYCO1, MID2

Annotation Cluster 3 Enrichment Score: 1.1276637957883262

GO:0000075 cell cycle checkpoint 0.010137 TAOK1, GIGYF2, BUB3, FOXN3, ATF2 FBXW7, GSPT1, TAOK1, KIAA0430, CLIP1, TUBE1, GO:0022402 cell cycle process 0.010174 GIGYF2, USP33, BUB3, FOXN3, EML4, ATF2

GO:0000077 DNA damage checkpoint 0.017372 TAOK1, GIGYF2, FOXN3, ATF2 TAOK1, KIAA0430, FOXN3, EML4, ATF2, FBXW7, GO:0007049 cell cycle 0.017944 GSPT1, PAK2, CLIP1, TUBE1, USP33, GIGYF2, BUB3

GO:0031570 DNA integrity checkpoint 0.020624 TAOK1, GIGYF2, FOXN3, ATF2

GO:0007093 mitotic cell cycle checkpoint 0.020967 GIGYF2, BUB3, FOXN3, ATF2

GO:0045930 negative regulation of mitotic cell cycle 0.047204 GIGYF2, BUB3, FOXN3, ATF2

Annotation Cluster 4 Enrichment Score: 1.0524732568167308 DYNC1LI2, VIM, KIAA0430, ATF2, ABCA5, SSR1, FBXW7, TMED2, PAK2, IL1RAP, TBC1D5, TUBE1, SCARB2, SAR1B, USP33, FYCO1, AKT3, BUB3, RAB8B, TAOK1, RYK, SF1, EML4, FBXO38, BBS2, GO:0016043 cellular component organization 0.03475 ADNP2, BAZ1B, GSPT1, CELF2, CLIP1, ABL2 DYNC1LI2, RAB8B, TAOK1, VIM, KIAA0430, ATF2, EML4, BBS2, FBXW7, BAZ1B, TMED2, TBC1D5, CLIP1, TUBE1, SCARB2, SAR1B, ABL2, FYCO1, GO:0006996 organelle organization 0.046543 USP33, BUB3, AKT3 DYNC1LI2, VIM, KIAA0430, ATF2, ABCA5, SSR1, FBXW7, TMED2, PAK2, IL1RAP, TBC1D5, TUBE1, SCARB2, SAR1B, USP33, FYCO1, AKT3, BUB3, cellular component organization or RAB8B, TAOK1, RYK, SF1, EML4, FBXO38, BBS2, GO:0071840 biogenesis 0.04844 ADNP2, BAZ1B, GSPT1, CELF2, CLIP1, ABL2

Annotation Cluster 5 Enrichment Score: 0.9254147029064898 regulation of cell projection FBXO38, RAB8B, RYK, VIM, IL1RAP, TBC1D5, CLIP1, GO:0031344 organization 0.004985 ABL2 regulation of neuron projection GO:0010975 development 0.018065 FBXO38, RYK, VIM, IL1RAP, CLIP1, ABL2 FBXO38, BBS2, RAB8B, PAK2, RYK, VIM, IL1RAP, GO:0030030 cell projection organization 0.020064 TBC1D5, CLIP1, ABL2, USP33 positive regulation of cell projection GO:0031346 organization 0.02586 FBXO38, RAB8B, IL1RAP, CLIP1, ABL2 FBXO38, PAK2, RYK, VIM, IL1RAP, CLIP1, ABL2, GO:0031175 neuron projection development 0.030331 USP33 FBXO38, ADNP2, PAK2, RYK, VIM, IL1RAP, CLIP1, GO:0030182 neuron differentiation 0.035135 GIGYF2, ABL2, USP33

Annotation Cluster 6 Enrichment Score: 0.9097209940740182 CAMTA1, EIF4E3, PHLPP2, FKBP5, VIM, KIAA0430, CASK, ZNF652, ATF2, DDI2, G2E3, FBXW7, TMED2, PAK2, ZNF224, IL1RAP, MIER3, TBC1D5, PER3, USP33, TNRC6A, RPRD1A, AKT3, BUB3, CAPN7, RCOR3, TAOK1, RYK, SF1, SOCS5, FOXN3, ELL2, MID2, FEM1C, PJA2, BBS2, PCF11, ADNP2, BAZ1B, GSPT1, PTAR1, GFPT1, CELF2, C2ORF49, ABL2, GO:0043170 macromolecule metabolic process 0.001037 GIGYF2, ZNF382 CAMTA1, EIF4E3, KIAA0430, VIM, CASK, ZNF652, ATF2, FBXW7, TMED2, ZNF224, MIER3, IL1RAP, PER3, TNRC6A, RPRD1A, RCOR3, SF1, FOXN3, ELL2, MID2, BBS2, ADNP2, BAZ1B, GFPT1, GIGYF2, GO:0010468 regulation of gene expression 0.008941 ZNF382 CAMTA1, EIF4E3, VIM, KIAA0430, CASK, ZNF652, ATF2, FBXW7, TMED2, PAK2, ZNF224, MIER3, IL1RAP, TBC1D5, PER3, TNRC6A, RPRD1A, BUB3, RCOR3, TAOK1, RYK, SF1, SOCS5, FOXN3, ELL2, regulation of macromolecule metabolic MID2, BBS2, ADNP2, BAZ1B, GFPT1, GIGYF2, GO:0060255 process 0.008953 ZNF382 CAMTA1, EIF4E3, VIM, KIAA0430, CASK, ZNF652, ATF2, FBXW7, TMED2, PAK2, ZNF224, MIER3, IL1RAP, TBC1D5, PER3, TNRC6A, RPRD1A, BUB3, RCOR3, TAOK1, RYK, SF1, SOCS5, FOXN3, ELL2, MID2, BBS2, ADNP2, BAZ1B, GFPT1, ABL2, GIGYF2, GO:0019222 regulation of metabolic process 0.011749 ZNF382 CAMTA1, EIF4E3, PHLPP2, FKBP5, KIAA0430, CASK, ZNF652, ATF2, G2E3, FBXW7, PAK2, ZNF224, IL1RAP, MIER3, TBC1D5, PER3, USP33, TNRC6A, RPRD1A, AKT3, BUB3, RCOR3, TAOK1, RYK, SF1, SOCS5, FOXN3, ELL2, MID2, FEM1C, PJA2, PCF11, cellular macromolecule metabolic ADNP2, BAZ1B, GSPT1, PTAR1, CELF2, C2ORF49, GO:0044260 process 0.014544 ABL2, GIGYF2, ZNF382 CAMTA1, EIF4E3, VIM, CASK, ZNF652, ATF2, FBXW7, TMED2, ZNF224, MIER3, IL1RAP, PER3, TNRC6A, RPRD1A, RCOR3, SF1, FOXN3, ELL2, MID2, PCF11, BBS2, ADNP2, BAZ1B, GSPT1, GO:0010467 gene expression 0.017106 GFPT1, C2ORF49, CELF2, GIGYF2, ZNF382 negative regulation of macromolecule FBXW7, RCOR3, ZNF224, SF1, PER3, GIGYF2, GO:0010558 biosynthetic process 0.033922 TNRC6A, ZNF382, FOXN3, ATF2, MID2 RCOR3, KIAA0430, SF1, SOCS5, FOXN3, MID2, negative regulation of metabolic ATF2, BBS2, FBXW7, PAK2, ZNF224, PER3, GIGYF2, GO:0009892 process 0.038268 TNRC6A, BUB3, ZNF382 RCOR3, SF1, SOCS5, FOXN3, MID2, ATF2, BBS2, negative regulation of macromolecule FBXW7, PAK2, ZNF224, PER3, GIGYF2, TNRC6A, GO:0010605 metabolic process 0.041577 ZNF382, BUB3 negative regulation of cellular FBXW7, RCOR3, ZNF224, SF1, PER3, GIGYF2, GO:0031327 biosynthetic process 0.043543 TNRC6A, ZNF382, FOXN3, ATF2, MID2 RCOR3, KIAA0430, SF1, SOCS5, FOXN3, MID2, negative regulation of cellular ATF2, FBXW7, PAK2, ZNF224, PER3, GIGYF2, GO:0031324 metabolic process 0.044105 TNRC6A, ZNF382, BUB3 negative regulation of biosynthetic FBXW7, RCOR3, ZNF224, SF1, PER3, GIGYF2, GO:0009890 process 0.047731 TNRC6A, ZNF382, FOXN3, ATF2, MID2 negative regulation of nitrogen FBXW7, RCOR3, ZNF224, SF1, PER3, GIGYF2, GO:0051172 compound metabolic process 0.048092 TNRC6A, ZNF382, FOXN3, ATF2, MID2

Annotation Cluster 7 Enrichment Score: 0.7138986023041735

GO:0007062 sister chromatid cohesion 0.011798 FBXW7, TAOK1, CLIP1, BUB3

GO:0000819 sister chromatid segregation 0.049886 FBXW7, TAOK1, CLIP1, BUB3

Annotation Cluster 8 Enrichment Score: 0.5802981069084664 establishment of protein localization to GO:0090150 membrane 0.046903 BBS2, RAB8B, TMED2, CLIP1, SSR1

Annotation Cluster 9 Enrichment Score: 0.42916203800540753

GO:0018108 peptidyl-tyrosine phosphorylation 0.009263 FBXW7, PAK2, BAZ1B, RYK, SOCS5, ABL2

GO:0018212 peptidyl-tyrosine modification 0.00948 FBXW7, PAK2, BAZ1B, RYK, SOCS5, ABL2

Annotation Cluster 10 Enrichment Score: 0.40498640863411367

GO:0018108 peptidyl-tyrosine phosphorylation 0.009263 FBXW7, PAK2, BAZ1B, RYK, SOCS5, ABL2

GO:0018212 peptidyl-tyrosine modification 0.00948 FBXW7, PAK2, BAZ1B, RYK, SOCS5, ABL2 CAMTA1, EIF4E3, PHLPP2, FKBP5, KIAA0430, CASK, ZNF652, ATF2, G2E3, FBXW7, PAK2, ZNF224, IL1RAP, MIER3, TBC1D5, PER3, USP33, TNRC6A, RPRD1A, AKT3, BUB3, RCOR3, TAOK1, RYK, SF1, SOCS5, FOXN3, ELL2, MID2, FEM1C, PJA2, PCF11, cellular macromolecule metabolic ADNP2, BAZ1B, GSPT1, PTAR1, CELF2, C2ORF49, GO:0044260 process 0.014544 ABL2, GIGYF2, ZNF382 regulation of protein tyrosine kinase GO:0061097 activity 0.023351 FBXW7, PAK2, SOCS5

Table S4. Gene ontology enrichment based on cellular component term for up-regulated DEGs. They were selected with P-value < 0.05 as the significant cellular component. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes Annotation Enrichment Score: Cluster 1 3.2106202680239373 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, SOCS5, FOXN3, ELL2, EML4, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, EIF4E3, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, MSI2, SLC39A6, PER3, SCARB2, USP33, intracellular TNRC6A, FYCO1, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, RYK, MID2, FBXO38, GO:0044424 part 3.25E-06 FEM1C, ADNP2, GSPT1, PTAR1, GFPT1, FNBP4, C2ORF49, KATNBL1, ABL2 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, SOCS5, FOXN3, ELL2, EML4, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, EIF4E3, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, MSI2, SLC39A6, PER3, SCARB2, USP33, TNRC6A, FYCO1, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, RYK, MID2, FBXO38, GO:0005622 intracellular 1.41E-05 FEM1C, ADNP2, GSPT1, PTAR1, GFPT1, FNBP4, C2ORF49, KATNBL1, ABL2 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, FOXN3, ELL2, EML4, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, SLC39A6, PER3, SCARB2, TNRC6A, FYCO1, USP33, BUB3, intracellular CAPN7, RAB8B, TM2D1, RYK, MID2, FBXO38, FEM1C, ADNP2, FNBP4, GO:0043229 organelle 2.03E-04 C2ORF49, KATNBL1, ABL2 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, FOXN3, ELL2, EML4, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, SLC39A6, PER3, SCARB2, TNRC6A, FYCO1, USP33, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, RYK, MID2, FBXO38, FEM1C, ADNP2, GFPT1, GO:0043226 organelle 6.12E-04 FNBP4, C2ORF49, KATNBL1, ABL2 KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, FOXN3, ELL2, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, ZNF382, CAMTA1, PHLPP2, FKBP5, VIM, membrane- ZNF652, ATF2, ABCA5, FBXW7, TMED2, ZNF224, TBC1D5, SLC39A6, PER3, bounded SCARB2, TNRC6A, FYCO1, USP33, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, GO:0043227 organelle 0.005607096 RYK, MID2, FEM1C, FBXO38, ADNP2, GFPT1, FNBP4, C2ORF49, KATNBL1 KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, MIER3, SAR1B, RPRD1A, IFNGR1, AKT3, METTL8, RCOR3, SF1, FOXN3, ELL2, PJA2, PCF11, intracellular BAZ1B, CLIP1, CELF2, ZNF382, CAMTA1, PHLPP2, FKBP5, VIM, ZNF652, membrane- ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, SLC39A6, SCARB2, PER3, bounded USP33, TNRC6A, FYCO1, BUB3, CAPN7, RAB8B, TM2D1, RYK, FBXO38, GO:0043231 organelle 0.006789505 FEM1C, ADNP2, FNBP4, C2ORF49, KATNBL1 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, IL1RAP, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, SOCS5, FOXN3, EML4, ELL2, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, EIF4E3, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, MSI2, SLC39A6, PER3, SCARB2, USP33, TNRC6A, FYCO1, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, RYK, MID2, FBXO38, FEM1C, ADNP2, GSPT1, PTAR1, GFPT1, FNBP4, C2ORF49, GO:0044464 cell part 0.00929746 KATNBL1, ABL2 DYNC1LI2, KIAA0430, DNAJB14, CASK, SSR1, DDI2, G2E3, PAK2, IL1RAP, MIER3, SAR1B, RPRD1A, AKT3, IFNGR1, METTL8, RCOR3, SF1, SOCS5, FOXN3, EML4, ELL2, PJA2, BBS2, PCF11, BAZ1B, CELF2, CLIP1, GPATCH11, ZNF382, CAMTA1, EIF4E3, PHLPP2, FKBP5, VIM, ZNF652, ABCA5, ATF2, FBXW7, TMED2, ZNF224, TBC1D5, TUBE1, MSI2, SLC39A6, PER3, SCARB2, USP33, TNRC6A, FYCO1, BUB3, CAPN7, RAB8B, TM2D1, TAOK1, RYK, MID2, GO:0005623 cell 0.010280442 FBXO38, FEM1C, ADNP2, GSPT1, PTAR1, GFPT1, FNBP4, C2ORF49, KATNBL1, ABL2 Annotation Enrichment Score: Cluster 2 1.6912595452292345 CAMTA1, PHLPP2, FKBP5, CASK, ZNF652, ATF2, DDI2, G2E3, FBXW7, PAK2, ZNF224, MIER3, PER3, USP33, TNRC6A, RPRD1A, AKT3, BUB3, CAPN7, METTL8, RCOR3, TM2D1, RYK, SF1, FOXN3, ELL2, FEM1C, FBXO38, PCF11, GO:0005634 nucleus 0.006333873 ADNP2, BAZ1B, FNBP4, CELF2, C2ORF49, CLIP1, KATNBL1, ZNF382 CAPN7, TM2D1, FKBP5, SF1, CASK, ELL2, ATF2, DDI2, FEM1C, PCF11, G2E3, FBXW7, PAK2, BAZ1B, ZNF224, FNBP4, CLIP1, C2ORF49, KATNBL1, RPRD1A, GO:0044428 nuclear part 0.010470204 TNRC6A, USP33, BUB3, AKT3 DYNC1LI2, PHLPP2, FKBP5, VIM, DNAJB14, CASK, ATF2, ABCA5, SSR1, DDI2, G2E3, FBXW7, TMED2, PAK2, ZNF224, TBC1D5, TUBE1, SCARB2, SAR1B, TNRC6A, RPRD1A, USP33, AKT3, BUB3, CAPN7, RAB8B, TM2D1, SF1, ELL2, EML4, MID2, FEM1C, PJA2, BBS2, PCF11, BAZ1B, FNBP4, C2ORF49, CLIP1, GO:0044422 organelle part 0.012845149 KATNBL1, GPATCH11 CAPN7, TM2D1, FKBP5, SF1, CASK, ELL2, ATF2, DDI2, FEM1C, PCF11, G2E3, FBXW7, PAK2, BAZ1B, FNBP4, C2ORF49, KATNBL1, RPRD1A, TNRC6A, GO:0031981 nuclear lumen 0.013310927 USP33, BUB3, AKT3 DYNC1LI2, FKBP5, VIM, DNAJB14, CASK, ATF2, ABCA5, SSR1, DDI2, G2E3, FBXW7, TMED2, PAK2, ZNF224, TBC1D5, TUBE1, SCARB2, SAR1B, TNRC6A, RPRD1A, USP33, AKT3, BUB3, CAPN7, RAB8B, TM2D1, SF1, ELL2, EML4, intracellular MID2, FEM1C, PJA2, BBS2, PCF11, BAZ1B, FNBP4, C2ORF49, CLIP1, GO:0044446 organelle part 0.015894324 KATNBL1, GPATCH11 CAPN7, TM2D1, FKBP5, SF1, ELL2, ATF2, DDI2, FEM1C, PCF11, FBXW7, GO:0005654 nucleoplasm 0.01776202 PAK2, BAZ1B, FNBP4, C2ORF49, RPRD1A, TNRC6A, USP33, BUB3, AKT3 intracellular CAPN7, TM2D1, FKBP5, SF1, CASK, ELL2, ATF2, DDI2, FEM1C, PCF11, G2E3, organelle FBXW7, PAK2, BAZ1B, FNBP4, C2ORF49, KATNBL1, SCARB2, RPRD1A, GO:0070013 lumen 0.049428997 TNRC6A, USP33, BUB3, AKT3 Annotation Enrichment Score: Cluster 3 1.216796438172573 intracellular non- membrane- DYNC1LI2, VIM, SF1, CASK, ELL2, ATF2, MID2, EML4, PJA2, BBS2, G2E3, bounded FBXW7, BAZ1B, CLIP1, TUBE1, KATNBL1, ABL2, TNRC6A, GPATCH11, USP33, GO:0043232 organelle 0.043339962 BUB3, IFNGR1 non- membrane- DYNC1LI2, VIM, SF1, CASK, ELL2, ATF2, MID2, EML4, PJA2, BBS2, G2E3, bounded FBXW7, BAZ1B, CLIP1, TUBE1, KATNBL1, ABL2, TNRC6A, GPATCH11, USP33, GO:0043228 organelle 0.043339962 BUB3, IFNGR1 Annotation Enrichment Score: Cluster 4 0.8390973620979801 chromosome, centromeric GO:0000775 region 0.031190343 BAZ1B, CLIP1, GPATCH11, BUB3 Annotation Enrichment Score: Cluster 5 0.5187880669643884 ciliary GO:0060170 membrane 0.0356323 BBS2, PHLPP2, CASK

Supplementary Table S5. Gene ontology enrichment based on molecular function term for up-regulated DEGs. They were selected with P-value < 0.05 as the significant molecular function. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes Annotation Enrichment Score: Cluster 1 2.050568947151532 CAMTA1, DYNC1LI2, EIF4E3, FKBP5, VIM, KIAA0430, CASK, ZNF652, ATF2, ABCA5, PAK2, ZNF224, MIER3, MSI2, TUBE1, SAR1B, TNRC6A, AKT3, RAB8B, heterocyclic RCOR3, TAOK1, RYK, SF1, FOXN3, ELL2, PCF11, ADNP2, BAZ1B, GSPT1, GO:1901363 compound binding 0.002676 CELF2, CLIP1, GPATCH11, ABL2, GIGYF2, ZNF382 CAMTA1, DYNC1LI2, EIF4E3, FKBP5, VIM, KIAA0430, CASK, ZNF652, ATF2, ABCA5, PAK2, ZNF224, MIER3, MSI2, TUBE1, SAR1B, TNRC6A, AKT3, RAB8B, organic cyclic RCOR3, TAOK1, RYK, SF1, FOXN3, ELL2, PCF11, ADNP2, BAZ1B, GSPT1, GO:0097159 compound binding 0.003442 CELF2, CLIP1, GPATCH11, ABL2, GIGYF2, ZNF382 CAMTA1, EIF4E3, RCOR3, KIAA0430, VIM, SF1, ZNF652, FOXN3, ELL2, ATF2, PCF11, ADNP2, GSPT1, ZNF224, MIER3, CLIP1, CELF2, MSI2, GIGYF2, GO:0003676 nucleic acid binding 0.07655 TNRC6A, GPATCH11, ZNF382 Annotation Enrichment Score: Cluster 2 1.0645761820305801 DYNC1LI2, RAB8B, RYK, TAOK1, KIAA0430, CASK, ABCA5, PAK2, BAZ1B, GO:0000166 nucleotide binding 0.014757 GSPT1, TUBE1, CELF2, MSI2, SAR1B, ABL2, TNRC6A, AKT3 nucleoside phosphate DYNC1LI2, RAB8B, RYK, TAOK1, KIAA0430, CASK, ABCA5, PAK2, BAZ1B, GO:1901265 binding 0.014812 GSPT1, TUBE1, CELF2, MSI2, SAR1B, ABL2, TNRC6A, AKT3 small molecule DYNC1LI2, RAB8B, RYK, TAOK1, KIAA0430, CASK, ABCA5, PAK2, BAZ1B, GO:0036094 binding 0.027923 GSPT1, TUBE1, CELF2, MSI2, SAR1B, ABL2, TNRC6A, AKT3 GO:0004672 protein kinase activity 0.036662 PAK2, BAZ1B, TAOK1, RYK, CASK, ABL2, AKT3 purine ribonucleoside DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0035639 triphosphate binding 0.042054 SAR1B, ABL2, AKT3 purine ribonucleoside DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0032550 binding 0.04341 SAR1B, ABL2, AKT3 purine nucleoside DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0001883 binding 0.043869 SAR1B, ABL2, AKT3 ribonucleoside DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0032549 binding 0.043869 SAR1B, ABL2, AKT3 DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0001882 nucleoside binding 0.044953 SAR1B, ABL2, AKT3 purine ribonucleotide DYNC1LI2, RAB8B, RYK, TAOK1, CASK, ABCA5, PAK2, GSPT1, BAZ1B, TUBE1, GO:0032555 binding 0.048815 SAR1B, ABL2, AKT3

Table S6. Gene ontology enrichment based on biological process term for down-regulated DEGs. They were selected with P value < 0.05 as the significant biological process. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes Annotation Cluster 1 Enrichment Score: 0.7613112520752194 TUFM, DTX1, AIF1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GO:0044267 cellular protein metabolic process 0.011896 GRK5, DAP, FARSA, MRPL45, B4GALT7, EIF4E2, HDAC7 AIF1, DTX1, PUSL1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, ACRC, GO:0043412 macromolecule modification 0.01846 PLA2G6, GRK5, B4GALT7, HDAC7 TUFM, DTX1, AIF1, COPRS, DUSP22, ANPEP, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GRK5, DAP, FARSA, MRPL45, B4GALT7, EIF4E2, GO:0019538 protein metabolic process 0.018791 HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, MEN1, UQCR11, ZNF324, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, TOX2, HDAC1, ARRB1, PLA2G6, GO:0006807 nitrogen compound metabolic process 0.019514 FARSA, MRPL45, KPNA2, HDAC7, EIF4E2 TUFM, DTX1, COPRS, CHST2, DUSP22, COMMD9, TOX2, MEN1, ZNF324, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GO:0009059 macromolecule biosynthetic process 0.021932 DAP, FARSA, MRPL45, B4GALT7, RHOG, EIF4E2, HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, ZNF324, ATG7, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, FARSA, GRK5, MRPL45, UBAP2, GO:0043170 macromolecule metabolic process 0.028871 KPNA2, EIF4E2, HDAC7 TUFM, DTX1, AIF1, COPRS, CHST2, DUSP22, COMMD9, TOX2, DAGLB, MEN1, ZNF324, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, DAP, FARSA, MRPL45, B4GALT7, RHOG, GO:0044249 cellular biosynthetic process 0.033903 EIF4E2, HDAC7 TUFM, DTX1, AIF1, PUSL1, COPRS, DUSP22, ANPEP, COMMD9, TOX2, MEN1, ZNF324, UQCR11, HDAC1, ARRB1, cellular nitrogen compound metabolic SETMAR, ACRC, PLA2G6, DAP, FARSA, MRPL45, KPNA2, GO:0034641 process 0.034934 RHOG, EIF4E2, HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, ABHD16A, ATG7, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, DAGLB, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, GO:0044237 cellular metabolic process 0.043685 FARSA, GRK5, MRPL45, KPNA2, EIF4E2, HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, ABHD16A, ATG7, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, FARSA, GRK5, MRPL45, UBAP2, KPNA2, GO:0008152 metabolic process 0.044952 EIF4E2, HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, ABHD16A, ATG7, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, DAGLB, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, GO:0044238 primary metabolic process 0.04675 FARSA, GRK5, MRPL45, KPNA2, EIF4E2, HDAC7 AIF1, DTX1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GRK5, GO:0006464 cellular protein modification process 0.047376 B4GALT7, HDAC7 AIF1, DTX1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GRK5, GO:0036211 protein modification process 0.047376 B4GALT7, HDAC7 TUFM, DTX1, AIF1, COPRS, CHST2, DUSP22, COMMD9, TOX2, DAGLB, MEN1, ZNF324, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, DAP, FARSA, MRPL45, B4GALT7, RHOG, GO:0009058 biosynthetic process 0.048575 EIF4E2, HDAC7 TUFM, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, ABHD16A, ATG7, SETMAR, ACRC, DAP, B4GALT7, RHOG, DTX1, CHST2, DUSP22, DAGLB, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, GO:0071704 organic substance metabolic process 0.04992 FARSA, GRK5, MRPL45, UBAP2, KPNA2, EIF4E2, HDAC7 Annotation Cluster 2 Enrichment Score: 0.7085147802867421

modification of morphology or physiology of other organism involved in symbiotic GO:0051817 interaction 0.023652 HDAC1, ATG7, KPNA2 modification of morphology or physiology GO:0035821 of other organism 0.033336 HDAC1, ATG7, KPNA2 Annotation Cluster 3 Enrichment Score: 0.5438770693729118 GO:0016570 histone modification 0.005122 MEN1, HDAC1, ARRB1, COPRS, SETMAR, HDAC7 GO:0016569 covalent chromatin modification 0.012772 MEN1, HDAC1, ARRB1, COPRS, SETMAR, HDAC7 MEN1, HIST1H2BK, HDAC1, ARRB1, COPRS, SETMAR, GO:0006325 chromatin organization 0.012912 HDAC7 GO:0090630 activation of GTPase activity 0.017421 TBC1D13, RHOG, TBC1D9B GO:0032092 positive regulation of protein binding 0.017839 MEN1, MFNG, ARRB1 TUFM, MAU2, AIF1, COPRS, MEN1, HIST1H2BK, HDAC1, ARRB1, ATG7, TBC1D13, SETMAR, PLA2G6, MRPL45, GO:0006996 organelle organization 0.019368 TUBA1A, RHOG, HDAC7, TBC1D9B GO:0018205 peptidyl-lysine modification 0.01994 MEN1, HDAC1, ARRB1, SETMAR, HDAC7 modification of morphology or physiology of other organism involved in symbiotic GO:0051817 interaction 0.023652 HDAC1, ATG7, KPNA2 GO:0071333 cellular response to glucose stimulus 0.026068 MEN1, ARRB1, PLA2G6 GO:0071331 cellular response to hexose stimulus 0.027564 MEN1, ARRB1, PLA2G6 cellular response to monosaccharide GO:0071326 stimulus 0.027564 MEN1, ARRB1, PLA2G6 MEN1, HIST1H2BK, MAU2, HDAC1, ARRB1, COPRS, GO:0051276 chromosome organization 0.029444 SETMAR, HDAC7 TMEM214, HDAC1, AIF1, ARRB1, ATG7, CDIP1, DUSP22, GO:0006915 apoptotic process 0.030391 PLA2G6, DAP, GRK5 cellular response to carbohydrate GO:0071322 stimulus 0.032253 MEN1, ARRB1, PLA2G6 modification of morphology or physiology GO:0035821 of other organism 0.033336 HDAC1, ATG7, KPNA2 GO:0001678 cellular glucose homeostasis 0.034432 MEN1, ARRB1, PLA2G6 TMEM214, HDAC1, AIF1, ARRB1, ATG7, CDIP1, DUSP22, GO:0012501 programmed cell death 0.042073 PLA2G6, DAP, GRK5 GO:0016571 histone methylation 0.0443 MEN1, COPRS, SETMAR AIF1, DTX1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GRK5, GO:0006464 cellular protein modification process 0.047376 B4GALT7, HDAC7 AIF1, DTX1, COPRS, DUSP22, UBE2R2, MEN1, PPM1G, RNF123, HDAC1, ARRB1, ATG7, SETMAR, PLA2G6, GRK5, GO:0036211 protein modification process 0.047376 B4GALT7, HDAC7 negative regulation of sequence-specific GO:0043433 DNA binding transcription factor activity 0.048006 MEN1, ARRB1, DAP GO:0051099 positive regulation of binding 0.0499 MEN1, MFNG, ARRB1

Table S7. Gene ontology enrichment based on cellular component term for down-regulated DEGs. They were selected with P-value < 0.05 as the significant cellular component. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes Annotation Enrichment Score: Cluster 1 1.2468139412886579 TUFM, MFNG, MAU2, TMEM214, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, HIST1H2BK, CDIP1, ATG7, TBC1D13, SETMAR, ACRC, TUBA1A, B4GALT7, RHOG, TBC1D9B, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, PPM1G, HDAC1, LASP1, ARRB1, PLA2G6, FARSA, GRK5, MRPL45, GO:0005622 intracellular 0.006865626 UBAP2, KPNA2, EIF4E2, HDAC7 intracellular TUFM, MFNG, MAU2, TMEM214, AIF1, COPRS, ANPEP, MEN1, UQCR11, HIST1H2BK, organelle ATG7, SETMAR, TUBA1A, B4GALT7, RHOG, CHST2, CYB561A3, DAGLB, TOX2, GO:0044446 part 0.022470941 PPM1G, HDAC1, LASP1, ARRB1, PLA2G6, GRK5, MRPL45, KPNA2, HDAC7 TUFM, MFNG, MAU2, TMEM214, AIF1, PUSL1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, ZNF324, HIST1H2BK, CDIP1, ATG7, SETMAR, ACRC, TUBA1A, B4GALT7, RHOG, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, intracellular PPM1G, HDAC1, LASP1, ARRB1, PLA2G6, FARSA, GRK5, MRPL45, UBAP2, KPNA2, GO:0044424 part 0.030520792 EIF4E2, HDAC7 TUFM, MFNG, MAU2, TMEM214, AIF1, COPRS, ANPEP, MEN1, UQCR11, HIST1H2BK, organelle ATG7, SETMAR, TUBA1A, B4GALT7, RHOG, CHST2, CYB561A3, DAGLB, TOX2, GO:0044422 part 0.030665372 PPM1G, HDAC1, LASP1, ARRB1, PLA2G6, GRK5, MRPL45, KPNA2, HDAC7 intracellular TUFM, MFNG, MAU2, TMEM214, AIF1, PUSL1, COPRS, ANPEP, COMMD9, MEN1, membrane- UQCR11, ZNF324, HIST1H2BK, CDIP1, SETMAR, ACRC, TUBA1A, B4GALT7, RHOG, bounded DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, PPM1G, HDAC1, ARRB1, PLA2G6, GO:0043231 organelle 0.032583384 GRK5, MRPL45, UBAP2, KPNA2, HDAC7 TUFM, MFNG, MAU2, TMEM214, AIF1, PUSL1, COPRS, ANPEP, COMMD9, MEN1, UQCR11, ZNF324, HIST1H2BK, CDIP1, ATG7, SETMAR, ACRC, TUBA1A, B4GALT7, intracellular RHOG, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, PPM1G, HDAC1, LASP1, GO:0043229 organelle 0.041562316 ARRB1, PLA2G6, GRK5, MRPL45, UBAP2, KPNA2, HDAC7 TUFM, MFNG, TMEM214, AIF1, COPRS, ANPEP, COMMD9, UBE2R2, MEN1, RNF123, UQCR11, HIST1H2BK, ATG7, TUBA1A, B4GALT7, RHOG, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, PPM1G, HDAC1, LASP1, ARRB1, PLA2G6, FARSA, GRK5, GO:0005737 cytoplasm 0.043762341 MRPL45, UBAP2, KPNA2, EIF4E2, HDAC7 TUFM, MFNG, MAU2, TMEM214, AIF1, PUSL1, COPRS, ANPEP, COMMD9, MEN1, membrane- TEX264, UQCR11, ZNF324, HIST1H2BK, CDIP1, SETMAR, ACRC, TUBA1A, B4GALT7, bounded RHOG, DTX1, CHST2, DUSP22, CYB561A3, DAGLB, TOX2, PPM1G, HDAC1, LASP1, GO:0043227 organelle 0.049435662 ARRB1, PLA2G6, GRK5, MRPL45, UBAP2, KPNA2, HDAC7 Annotation Enrichment Score: Cluster 2 0.8089413292152717 lysosomal GO:0005765 membrane 0.032702411 ARRB1, ANPEP, CYB561A3, DAGLB lytic vacuole GO:0098852 membrane 0.032702411 ARRB1, ANPEP, CYB561A3, DAGLB Annotation Enrichment Score: Cluster 3 0.6133760078224594 chromosomal GO:0044427 part 0.047964207 MEN1, HIST1H2BK, MAU2, HDAC1, ARRB1, SETMAR Annotation Enrichment Score: Cluster 4 0.5261196476214102

GO:0000785 chromatin 0.026676097 MEN1, HIST1H2BK, MAU2, HDAC1, ARRB1 chromosomal GO:0044427 part 0.047964207 MEN1, HIST1H2BK, MAU2, HDAC1, ARRB1, SETMAR

Table S8. Gene ontology enrichment based on molecular function term for down-regulated DEGs. They were selected with P-value < 0.05 as the significant molecular function. Enrichment Score is related the type of analysis in DAVID database with selecting "functional annotation clustering" for analysis of gene lists.

Category Term P-Value Genes Enrichment Score: Annotation Cluster 1 1.3511771980019578

GO:0016298 lipase activity 0.040325338 ABHD16A, PLA2G6, DAGLB PPM1G, ABHD16A, SETMAR, DUSP22, GO:0016788 hydrolase activity, acting on ester bonds 0.042923883 PLA2G6, DAGLB Enrichment Score: Annotation Cluster 2 0.5764436200834914

GO:0043566 structure-specific DNA binding 0.049216187 MEN1, HDAC1, SETMAR