Supplementary Table 1. Significantly Upregulated in Expression in Retina Compared to FVMs Fold Description RefSeq P -value Symbol change Visual perception BEST1 NM_004183.2 4.07E-09 86.99 Retinal pigment epithelium-specific 65kDa RPE65 NM_000329.2 1.70E-10 86.03 Retinaldehyde binding protein 1 RLBP1 NM_000326.3 3.42E-07 84.89 Retinal G protein coupled RGR NM_001012720.18.61E-09 55.26 Tyrosinase (oculocutaneous albinism IA) TYR NM_000372.4 1.94E-11 43.54 Carbonic anhydrase IV CA4 NM_000717.2 1.46E-06 36.98 Opticin OPTC NM_014359.3 4.78E-08 32.73 Retinol dehydrogenase 5 (11-cis/9-cis) RDH5 NM_002905.2 6.41E-07 26.23 Secreted frizzled-related protein 5 SFRP5 NM_003015.2 2.31E-08 25.48 Retinal outer segment 1 ROM1 NM_000327.2 2.33E-06 15.08 Paired box 6, transcript variant 2 PAX6 NM_001604.3 1.03E-06 15.02 Bestrophin 2 BEST2 NM_017682.2 4.10E-09 12.70 Solute carrier family 45, member 2, transcript variant 1 SLC45A2 NM_016180.3 8.30E-09 12.12 Retina and anterior neural fold homeobox RAX NM_013435.2 7.62E-06 10.93 Retinol dehydrogenase 10 (all-trans) RDH10 NM_172037.2 1.34E-05 10.35 Retinal pigment epithelium-derived rhodopsin homolog RRH NM_006583.2 1.07E-06 10.16 Amine oxidase, copper containing 2 (retina-specific) AOC2 NM_001158.3 1.92E-08 9.48 Nervous system development Purkinje cell protein 4 PCP4 NM_006198.2 1.33E-05 70.59 Aldehyde dehydrogenase 1 family, member A2 ALDH1A2 NM_170697.1 5.08E-08 32.32 CD24 molecule CD24 NM_013230.2 1.46E-06 26.74 Endothelin 3 EDN3 NM_207032.1 1.89E-07 20.69 Cholinergic receptor, nicotinic, alpha 3. CHRNA3 NM_000743.2 1.24E-07 20.44 Cadherin 1, type 1, E-cadherin (epithelial) CDH1 NM_004360.2 1.47E-10 19.71 SRY (sex determining region Y)-box 10 SOX10 NM_006941.3 1.40E-08 18.40 Fas apoptotic inhibitory molecule 2 FAIM2 NM_012306.2 1.31E-05 15.84 Paired-like homeodomain 2 PITX2 NM_000325.5 2.63E-08 13.76 5 (neuroglycan C) CSPG5 NM_006574.3 1.09E-08 11.41 RELN NM_173054.1 2.62E-07 10.15 NDRG family member 2 NDRG2 NM_201539.1 1.39E-05 9.86 Microtubule-associated protein tau MAPT NM_016841.2 5.61E-06 9.37 Transcription factor AP-2 alpha (activating enhancer TFAP2A NM_001032280.23.27E-10 9.36 binding protein 2 alpha) Metabolism 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 HMGCS2 NM_005518.2 1.68E-09 57.48 (mitochondrial) Beta-carotene 15,15'-monooxygenase 1 BCMO1 NM_017429.2 5.50E-08 40.13 Solute carrier family 16, member 8 (monocarboxylic SLC16A8 NM_013356.2 1.49E-08 36.63 acid transporter 3) Apolipoprotein D APOD NM_001647.2 1.30E-05 36.59 Hydroxysteroid (17-beta) dehydrogenase 2 HSD17B2 NM_002153.1 1.86E-08 27.33 Creatine kinase, muscle CKM NM_001824.2 7.76E-10 17.97 ATPase, H+ transporting, lysosomal 42kDa, V1 ATP6V1C2 NM_144583.3 3.47E-09 16.28 ATPase, Na+/K+ transporting, beta 1 polypeptide ATP1B1 NM_001677.3 3.03E-07 13.73 -related peptidase 1 KLK11 NM_144947.1 1.28E-08 12.52 Solute carrier family 23 (nucleobase transporters), SLC23A2 NM_203327.1 9.22E-09 11.62 member 2 Carbonic anhydrase XIV CA14 NM_012113.1 7.77E-09 10.63 ATPase, class V, type 10B ATP10B NM_025153.2 7.15E-09 10.15 alpha/beta 1 TPSAB1 NM_003294.3 1.33E-06 9.82 Transport Transthyretin (prealbumin, amyloidosis type I) TTR NM_000371.1 5.79E-11 261.60 Solute carrier family 39 (zinc transporter), member 12 SLC39A12 NM_152725.2 5.31E-11 33.92 Chloride intracellular channel 6 CLIC6 NM_053277.1 6.36E-06 28.99 Transient receptor potential cation channel, subfamily TRPM3 NM_206948.2 4.55E-10 20.14 M, member 3

Downloaded from iovs.arvojournals.org on 10/02/2021 , nonvoltage-gated 1 alpha SCNN1A NM_001038.4 8.88E-08 20.13 Potassium inwardly-rectifying channel, subfamily J, KCNJ13 NM_002242.2 7.96E-08 16.77 member 13 Solute carrier family 29 (nucleoside transporters), SLC29A4 NM_153247.1 2.32E-08 15.68 member 4. Solute carrier family 13 (sodium/sulfate symporters), SLC13A4 NM_012450.2 1.07E-08 13.20 member 4 Snaptoporin SYNPR NM_144642.3 3.31E-07 12.80 Solute carrier family 7, (neutral transporter, SLC7A10 NM_019849.1 2.23E-08 11.68 y+ system) member 10 Solute carrier family 22 (organic anion transporter), SLC22A8 NM_004254.2 2.61E-07 10.57 member 8 Cell differentiation silver homolog (mouse) SILV NM_006928.3 9.50E-11 195.09 Tyrosinase-related protein 1 TYRP1 NM_000550.1 1.70E-12 127.86 Paired-like homeodomain transcription factor 1 PITX1 NM_002653.3 1.69E-10 59.19 Scavenger receptor class A, member 5 (putative) SCARA5 NM_173833.4 2.23E-09 32.14 Dopachrome tautomerase (dopachrome delta- DCT NM_001922.2 3.47E-10 25.96 , tyrosine-related protein 2). Collagen, type IX, alpha 1,transcript variant 1 COL9A1 NM_001851.3 9.23E-10 20.14 melanophilin MLPH NM_001042467.15.79E-08 20.10 Glyceraldehyde-3-phosphate dehydrogenase, GAPDHS NM_014364.3 3.12E-09 19.99 spermatogenic Death associated protein-like 1 DAPL1 NM_001017920.15.26E-06 16.89 ATPase, Ca++ transporting, cardiac muscle, fast ATP2A1 NM_173201.2 2.30E-10 16.63 Cbp/p300-interacting transactivator, with Glu/Asp-rich CITED1 NM_004143.2 4.80E-08 15.58 carboxy-terminal domain, 1 EGF-like-domain, multiple 6 EGFL6 NM_015507.2 4.85E-06 14.95 Folate receptor 1 (adult) FOLR1 NM_016724.1 6.05E-08 13.79 4 open reading frame 31 C4orf31 NM_024574.3 9.11E-08 13.17 Septin 3 SEPT3 NM_019106.4 3.15E-07 9.74 Signaling Ectonucleotide pyrophosphatase/ 2 ENPP2 NM_001040092.11.50E-07 22.17 () Gastrin-releasing peptide GRP NM_001012513.15.67E-06 14.45 DNA-damage-inducible transcript 4-like DDIT4L NM_145244.2 1.36E-07 12.68 Proenkephalin PENK NM_006211.2 4.66E-08 9.39 Anatomical structure development Sclerostin domain containing 1 SOSTDC1 NM_015464.2 1.90E-10 21.94 Myocilin, trabecular meshwork inducible glucocorticoid MYOC NM_000261.1 6.98E-11 19.44 response Forkhead box Q1 FOXQ1 NM_033260.3 1.16E-05 9.53 Development LIM domain only 1 (rhombotin 1) LMO1 NM_002315.1 2.75E-09 15.24 Immune response C3 and PZP-like, alpha-2-macroglobulin domain CPAMD8 NM_015692.2 7.50E-09 11.03 Stress response pathway inhibitor 2 TFPI2 NM_006528.2 5.34E-10 14.24 Unknown Hypothetical protein LOC285016 LOC285016 NM_001002919.15.63E-12 61.44 Melan-A MLANA NM_005511.1 5.76E-10 54.58 Tetraspanin 10 TSPAN10 NM_031945.3 1.06E-08 50.66 Similar to F-box only protein 2 LOC342897 NM_001001414.11.04E-10 27.96 Chromosome 2 open reading frame 40 C2orf40 NM_032411.1 9.17E-07 19.66 Mo sapiens FLJ42875 protein FLJ42875 XM_932794.1 1.25E-09 16.51 Transmembrane protein with EGF-like and two TMEFF2 NM_016192.2 8.16E-10 15.30 follistatin-like domains 2 CDNA FLJ38396 fis, clone FEBRA2007957 EST AK095715 1.07E-05 14.81 Reprimo-like RPRML NM_203400.1 7.86E-10 11.18

Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 2. Top Key Biological Functions Related to Genes Upregulated in Expression in FVMs Compared to Retina Focus Functions Molecules in Network Score Molecules ADAMTS9,ANXA2,C1q,CD93,COL1A2,COL1A1 (includes EG:1277),COL4A1,collagen, Connective Tissue Disorders, Cellular Collagen Alpha1,Cyclin D,Ecm,ECM1(includesEG:100332249), ERK1/2,FAP,Fibrin, Assembly and Organization, Cellular HSD11B2,IGFBP3,Igfbp,IL-1R,ITGA11,LOX,LRRC32,MMP11,Nuclear 41 22 Function and Maintenance factor1,POSTN,SH2B3,Smad2/3, Smad2/3Smad4,SPRY4,SULF1,TFPI,Tgf beta,TNC (includes EG:116640),TRAM2,VCAN Alpha catenin,CCNB2,COL3A1,COL4A2,COL5A1,COL5A2,COL6A3,Collagen type I, Cell Morphology, Cellular Assembly and Collagen type III,Collagen type IV,Collagen Type V,Collagen Type VI,Collagen(s),GPIIB- Organization, Hair and Skin Development IIIA,, beta 1, beta 1, beta 35 18 and Function 1,Integrin,ITGA1,LAMA4,LAMB1,LAMC1,Laminin1,Laminin2,Laminin,LUM,MMP23B,NFkB (complex),PLAU,SERPINH1,THBS1,THBS2, THY1,TNFAIP6

Humoral Immune Response, Cellular 14-3-3,Actin,Akt,Alp,APLN,Cadherin,CALD1,CDH5,CDH13,DLX5,ESM1,Ifn gamma,Ige, Growth and Proliferation, Hematological IL32,JAG1,Mlc,MYO1B,Nfat (family),NFE2L3,NOX4,Pak,PECAM1,PI3K (family),PIK3CG, 32 19 System Development and Function Rap1,Rock,TCR,TES,Tnf,TNFRSF4,TNFSF4,TOP2A,TPM4,Tropomyosin,TRPC6 Ca2+,CACNA2D2,CALU,CAST,EBF2,EEF1B2,FKBP2,FKBP8,FKBP1A,GIPR,GLP1R,HAS Cell-To-Cell Signaling and Interaction, 2,HAUS4,KDELR3,KISS1,NEFM,PAX3,PCSK6,PIN4 (includes EG:43044),POLA1, PPIC, Reproductive System Development and 28 15 PRND,PTMA,PXDN,RAI14,RPP40,SAMD9,TBX15,THBS2,TNC (includes EG:116640), Function, Cell Signaling TPPP3,UBC,USP6,WDR41,YY1 AHR,AVIL,C1QTNF6,C21orf7,CCL23,Ck2,COL14A1,CST1,DNTTIP1,ESR1,ETS1,FOXC1, Cell Morphology, Digestive System GEMIN2,Histone h3,HNF1A,IFNG (includes EG:15978),IL13,,Interferon alpha, Development and Function, Hepatic System 24 14 LRRC17,NR5A2,OLFML2A,OSM,PAMR1,PCDH17,POU4F1,Proinsulin,PWP2,RNA Development and Function polymerase II,SPATA18,ST8SIA4,SUMO2,TIMP4,TNFAIP8L1,TP53 (includes EG:22059) 26s Proteasome,Alpha tubulin,AMPK,CD36,CDKN1A,Cyclin A,Cytochrome c,DYSF,E2f, Cell Cycle, Cellular Development, Cellular estrogen receptor,Hdac,Histone h4,Ifn,IgG1,IgG,Igm,IL12 (complex),IL12 (family), 23 13 Growth and Proliferation Immunoglobulin,KRT7,N-cor,NLRP3,PHLDA2,PI3K (complex),PRSS23,RUNX1,Rxr, SETD8,SKA2,SP100,SRC (family),Tlr,TRPS1,TSH,UBE2C ANGPT2,Ap1, protein(s),Caspase 3/7,Cg,Collagen type IX,Creb,ERK, Organismal Injury and Abnormalities, Fibrinogen,FJX1,FSH,Growth hormone,HDL,IL1,INHBB,ITGB1,LDL,Lh,MAP2K1/2 16 10 Cardiac Fibrosis, Cardiovascular Disease ,Mek,MMP9,NADPH oxidase,Pdgf (complex),PDGF BB,Pkc(s),PTPRE,SERPINE1, Smad,Sos,SPARC,SPRED1,STAT5a/b,thyroid hormone receptor,Tnf receptor,TRIP11 ADCY,ADORA3,ANO1,Calmodulin,calpain,caspase,CD3,ENTPD1,F2R,FAM48A,FNDC1,F Organismal Injury and Abnormalities, ocal adhesion kinase,G protein alphai,G protein beta gamma,Gpcr,GPR116,Hsp90, 14 9 Respiratory Disease, Molecular Transport Jnk,Mapk,Mmp,P110,P38 MAPK,p85 (pik3r),Pka,PLC,PLC gamma,PPEF1,Pro- inflammatory Cytokine,Rac,Ras,Ras homolog,Sfk,Shc,TRAF6,Vegf

Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 3. Top Key Biological Functions Related to Genes Altered in Expression between Active and Inactive FVMs Focus Functions Molecules in Network Score Molecules Cell-To-Cell Signaling and AKAP12,Akt,Alp,ANGPT2,CEACAM1,CLDN11,Collagen Alpha1,CP, DLL4, GADD45B, GRB14,HEYL, Interaction, Cellular Compromise, LDL,LHX2,LINGO1, LYZ, MGST1,NADPH oxidase,NES,NOTCH3,Notch, NOX4, NR1H4,p70 S6k,Pdgf 48 24 Cardiovascular System Development (complex),PDGF BB,PDGFB,PLP1 (includes EG:18823), ROR2,SORCS1,SOX2,STAT5a/b,Tgf beta, 14-3-3,ADH1A,Alpha catenin,ATG16L1,C/ebp,CD36,CD48,CEBPD,CETP, DYSF, , Cancer, Reproductive System FBLN1,GAS1 (includes EG:14451),GFAP,Growth hormone,HDL, Hedgehog,Ige,IGF2, 45 23 Disease, Neurological Disease IL17RB,LAMA4,MAL,MYO1B,NFkB (complex), NFKBIZ, NID2, Nr1h,Nuclear factor 1,Pro-inflammatory Cardiovascular System Development Adaptor protein 1,APLN,ATP1A2,BMP6,C1q,C1R,C1S,CD34,COL10A1,Collagen type I, Collagen type II, and Function, Organismal Collagen type IV, Collagen type IX,Collagen(s),COMP,Complement component 1, DCN,ERK1/2,Ferritin, 37 20 Development, Tissue Development Fibrin, FMOD, GPC1, HLX, HSD11B2,INHBB,ITGA1, Laminin1,Laminin,OMD,RASD1,SEMA3F, AFAP1L1,Ap1,CaMKII,CCNF,CDH5,Cg,Creb,CRIP2,ERK,ESM1,ETS1,Fgf,FKBP1A, FSH,Gsk3,Histone Cellular Movement, Cancer, Tumor h3,LBH,Lh,MCAM,Mek, MMP9, Nfat (family),NMDA Receptor, NRCAM, Pka, PTP4A3,PTPase,PTPRA, 29 18 Morphology PTPRE, RASSF2,Rxr, SFRP1,SFRP4,SLC4A4, Vegf APOC4,AQP7,ARHGAP44,ARNT2,beta-estradiol,C13orf33,CACNA1I, CACNB1,CACNG1, Protein Synthesis, Small Molecule CHI3L2,CLEC4D, FAM124B,FMO2,GNB1,GNG11,GPX3,GSTT1,GYPA, MAN1C1,MC3R, 26 15 Biochemistry, Cell Cycle MGST1,NEBL,POPDC2, PPARG,Prl8a2, RAC1,ROBO4,RPL29 (includes EG:100039782), Cell Signaling, Embryonic ARHGEF17,CALML5,CASC5,CHST1,CXCR7,EDEM3,FAM101B,FBXL5,FZD2,FZD4,FZD6,GPR37,GRP Development, Organismal EL2,hemoglobin,IGF2BP2 ,LRRN2,MOXD1,NHP2L1,NSL1 (includes EG:25936), 24 14 Development NUP62CL,PCNX,PHAX,PLVAP,PRUNE, RPS4Y1, SMTN,SPC24 (includes Cancer, Cell-To-Cell Signaling and ADORA2A,Calmodulin,caspase,CD3,CRYAA,CXCR7,Cyclin A,DARC,estrogen receptor,F Interaction, Cellular Growth and Actin,FHOD1,Focal adhesion kinase,Gpcr,GPR37,Hdac,IKK (complex), Jnk,KCNJ2, 23 14 Proliferation KCNN2,LPAR1,Mapk,Mmp,OSR1,p85 (pik3r),PARVB,Pkc(s),PPEF1,Rac, Ras,Ras BAAT,BST1 (includes EG:12182),C1QB,C1R,CCL18,CCND1,CENPN,CFI,CLDN2, CTAG1B (includes others),FRMD4A,GAS1 (includes EG:14451),GSTT1,GYG2,HNF4A, IFNG (includes EG:15978),IKBKG, Cancer, Cell Cycle, Cell-To-Cell LMO3,miR-99a-5p (and other miRNAs w/seed ACCCGUA),NQO2,oleoyl-coenzyme A,OLFML3, 19 12 Signaling and Interaction PDIA5,POC1A,PPARA,PPT1, RARRES1,ROBO3,SCAMP5, STX2, TAF4 (includes EG:100149942), TAGLN2, TMEM204,TP53 (includes EG:22059),VAMP3 AMPK,CD69,collagen,CXADR,DOCK1,FGFR3,GOT,HLA-A,HLA-DRB1,HLA-DRB5, Hsp27, Cell Death and Survival, Cancer, Hsp70,Ifn,IFN Beta,IgG1,IgG,IgG2a,Igm,IL1,IL12 (complex),IL12 (family), Immunoglobulin, 15 10 Hematological Disease Integrin,Interferon alpha,MHC,MHC Class II (complex),NME1 (includes EG:18102),NOS2, P38 1-oleoyl-lysophosphatidic acid,1-palmitoyl-lysophosphatidic acid,Actin,ADCYAP1 (includes Cell Signaling, Molecular Transport, EG:11516),APLN,APP,C1QL1,Ca2+,CHAT,CRTAC1,cyclic AMP,D-glucose, dopamine, 13 9 Nucleic Acid Metabolism FXYD1,GAL,GFRA1,HADH,HAPLN1,Histone h4,HTR3A,Insulin,KCNF1, KCNH1,KCNN3, Ldh,MC3R,MFAP4,octanoic acid,PADI3,PFDN1,Proinsulin,RNA polymerase II,SLC2A9,

Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 4. Upstream regulators that can Modulate Expression Changes of the Genes upregulated in FVMs Compared to Retina Molecule Activation p -value of Upstream Regulator Target molecules in dataset Type z-score overlap Transcription regulator ANGPT2,CCNB2,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,COL4A2,COL5A1, MYC -3.201 1.42E-14 COL5A2,COL6A3,ECM1(includesEG:100332249),F2R,FAP,ITGB1,LOX,LUM,MYO1B,PLAU,SERPIN E1,SERPINH1,SPARC,TES,THBS1,THBS2,THY1,TNC (includes EG:116640),UBE2C CDKN1A,COL1A1(includesEG:1277),COL4A1,COL4A2,COL5A1,COL5A2,COL6A3,LAMC1,PLAU,SE SPDEF -2.714 5.15E-13 RPINE1,TNC (includes EG:116640) ANXA2,CALU,CCNB2,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,COL5A2,F2R TP53 3.08 8.61E-11 ,IGFBP3,LRRC17,MMP23B,MMP9,NOX4,PECAM1,PLAU,POSTN,PPIC,PTPRE,RUNX1,SERPINE1, SERPINH1,SPATA18,THBS1,THBS2,THY1,TOP2A,UBE2C,VCAN ANGPT2,CDKN1A,COL1A1(includesEG:1277),COL1A2,F2R,HSD11B2,IGFBP3,PLAU,SERPINE1,SE SP3 1.067 3.41E-10 RPINH1,SPARC,TNC (includes EG:116640),TNFRSF4 CDKN1A,COL4A1,COL5A1,F2R,IGFBP3,JAG1,PLAU,POSTN,RUNX1,SERPINE1,SH2B3,SPATA18, TP63 0.166 3.73E-10 THBS1,TNC (includes EG:116640) Chemical drug ADORA3,ANGPT2,CCNB2,CD36,CDH5,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL 4A1,COL4A2,COL5A1,COL5A2,F2R,IGFBP3,IL32,INHBB,ITGB1,JAG1,LAMB1,MMP23B,MMP9,NLR lipopolysaccharide 3.416 1.43E-16 P3,NR5A2,PECAM1,PIK3CG,PLAU,SERPINE1,SERPINH1,SPARC,TFPI,THBS1,THBS2,THY1,TNC(i ncludesEG:116640),TNFAIP6,TNFRSF4,TNFSF4,TOP2A,TRAF6,VCAN ramipril -2.828 4.17E-12 COL1A1 (includes EG:1277),COL1A2,COL3A1,COL4A1,COL4A2,LAMB1,LAMC1,MMP9 raloxifene 1.212 9.07E-11 CDKN1A,F2R,INHBB,ITGB1,KRT7,LAMB1,LUM,MYO1B,PLAU,PRSS23,PXDN,SERPINE1,TOP2A ANGPT2,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,F2R,FAP,ITGA1,ITGB1,MMP9,SER bleomycin 3.241 1.36E-10 PINE1,UBE2C ANXA2,CDH13,CDKN1A,COL1A2,COL3A1,COL6A3,IGFBP3,JAG1,KRT7,LOX,LUM,MMP9,PXDN,SE decitabine 3.89 5.26E-10 RPINH1,SPARC,THBS1,TOP2A,VCAN ANXA2,APLN,CALD1,CCNB2,CD36,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1 ,COL4A2,COL5A1,COL6A3,DLX5,ECM1(includesEG:100332249),ESM1,IGFBP3,INHBB,ITGA1,ITGB TGFB1 4.695 1.76E-17 1,JAG1,KDELR3,KRT7,LAMC1,LOX,MMP11,MMP9,NOX4,PECAM1,PHLDA2,PLAU,POSTN,RUNX1, SERPINE1,SERPINH1,SPARC,THBS1,THY1,TNC (includes EG:116640),TNFAIP6,TOP2A,VCAN ANGPT2,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,IGFBP3,ITGB1,LOX,MMP9,PLAU,P FGF2 2.962 1.23E-12 TPRE,RUNX1,SERPINE1,SPARC,SPRY4,TFPI,THBS1,TOP2A ANGPT2,APLN,CD36,CDH13,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,IGFB AGT 2.785 1.97E-12 P3,INHBB,ITGB1,JAG1,LAMB1,MMP9,NOX4,PLAU,POSTN,SERPINE1,TFPI CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,IGFBP3,ITGB1,MMP9,PHLDA2,PLAU,RUNX EGF 2.551 2.47E-10 1,SERPINE1,SH2B3,SPARC,SPRY4,THBS1,TNC (includes EG:116640),TNFRSF4,VCAN Group COL1A1(includesEG:1277),COL1A2,COL3A1,COL5A1,COL5A2,COL6A3,LAMA4,LUM,MMP11,MMP Alpha catenin -3.818 7.61E-16 23B,MMP9,PLAU,THBS2,TNC (includes EG:116640),TNFAIP6 CDKN1A,COL1A1(includesEG:1277),COL1A2,IGFBP3,ITGB1,JAG1,LOX,MMP11,MMP9,NOX4,PLAU Tgf beta 3.758 4.45E-12 ,POSTN,RUNX1,SERPINE1,SPARC CALD1,CDH13,CDH5,COL4A1,COL4A2,COL5A1,ITGB1,JAG1,KRT7,MMP9,PLAU,SERPINE1,SPAR estrogen receptor -1.648 2.93E-10 C,TNC (includes EG:116640) Kinase ADORA3,ANXA2,CCNB2,CD36,CDKN1A,COL1A1(includesEG:1277),COL3A1,COL4A1,COL5A1,CO ERBB2 0.915 2.28E-18 L5A2,COL6A3,F2R,IGFBP3,ITGB1,JAG1,KRT7,LAMB1,LUM,MMP11,MMP9,NOX4,PHLDA2,PLAU,S ERPINE1,SPARC,THBS1,TNC (includes EG:116640),TOP2A,UBE2C,VCAN ANGPT2,CDKN1A,COL1A1(includesEG:1277),COL3A1,COL5A2,F2R,FAP,HSD11B2,IGFBP3,JAG1, EGFR 1.958 4.59E-18 LAMA4,MMP9,PLAU,POSTN,PTPRE,RUNX1,SERPINE1,THBS1,TNC (includes Transmembrane receptor ANXA2,CD93,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,COL4A2,COL5A1,CO FAS 1.228 1.95E-13 L6A3,LUM,MMP9,PECAM1,PHLDA2,PIK3CG,PLAU,SERPINE1,TNC (includes ITGB1 -0.208 4.12E-10 CDKN1A,COL1A1(includes EG:1277),COL1A2,LAMB1,LAMC1,MMP9,PLAU,SERPINE1,THBS1 Translation regulator IGF2BP1 2.646 1.94E-11 COL1A1 (includes EG:1277),COL1A2,COL5A1,COL6A3,LUM,SERPINH1,TNC (includes EG:116640) Chemical - endogenous mammalian ANXA2,APLN,CD36,CD93,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,COL4A2, tretinoin 3.056 4.66E-11 IGFBP3,ITGA1,ITGB1,KRT7,LAMA4,LAMB1,LRRC32,MMP11,MMP9,PIK3CG,PLAU,POSTN,RAI14,S ERPINE1,SP100,SPARC,THBS1,TNC (includes EG:116640),TNFAIP6,TOP2A,TPM4,UBE2C Complex APLN,CDKN1A,ESM1,FJX1,HSD11B2,IGFBP3,INHBB,ITGA1,ITGB1,MMP9,NR5A2,PECAM1,PLAU, Cg 2.056 1.19E-10 RUNX1,TNFAIP6,VCAN Cytokine ANGPT2,APLN,CD36,CDH13,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,ESM1,IGFBP3, TNF 1.75 5.19E-11 IL32,ITGB1,JAG1,LAMA4,LAMC1,LOX,MMP9,NLRP3,NR5A2,PECAM1,PLAU,POSTN,PRSS23,SER PINE1,SPARC,TFPI,THBS1,THBS2,THY1,TNC (includes EG:116640),TNFAIP6,TNFRSF4,TRAF6 ANXA2,CALD1,CALU,CDKN1A,COL1A1(includesEG:1277),COL1A2,COL3A1,COL4A1,COL5A2,F2R, HRAS 1.024 6.64E-14 ITGB1,LRRC17,MMP23B,MMP9,PLAU,POSTN,PPIC,PRSS23,SERPINE1,SPARC,THBS1,TOP2A,T ITGAV 2.159 1.18E-11 CD36,CDKN1A,COL1A1 (includes EG:1277),COL1A2,ITGB1,MMP9,PLAU,SERPINE1 Mature microRNA miR-29b-3p -2.952 1.88E-10 COL1A1 (includes EG:1277),COL1A2,COL3A1,COL4A1,COL4A2,COL5A2,LAMC1,PPIC,SPARC Peptidase ADAMTS9,ANGPT2,CALD1,CDKN1A,COL1A1(includesEG:1277),COL4A1,ENTPD1,ESM1,F2R,IL32, F2 3.188 9.72E-11 ITGB1,MMP9,SERPINE1,TFPI,THBS1 Other COL1A1 (includes CR1L -3.138 1.88E-16 EG:1277),COL1A2,COL3A1,COL4A1,COL4A2,COL5A1,COL6A3,LUM,SERPINE1,TNC (includes COL4A3 1.91E-12 COL1A1 (includes EG:1277),COL1A2,COL3A1,COL4A1,COL4A2,LAMB1,LAMC1,MMP9 Positive values of Activation z-scores indicate activation of the target genes, and negative values indicate inhibiton of the target genes. P-values were detected by Fisher's exact tests.

Downloaded from iovs.arvojournals.org on 10/02/2021 Supplementary Table 5.Upstream regulators that can Modulate Expression Changes of the Genes Altered between Active and Inactive FVMs Molecule Upstream Activatio p -value of Target molecules in dataset Type Regulator n z-score overlap Transcription regulator HIF1A 0.783 1.92E-06 AKAP12,APLN,DLL4,ETS1,GADD45B,IGF2,INHBB,ITGA1,MMP9,NOS2,NOX4,PDGFB,TGFB3 CTNNB1 1.114 6.75E-06 CD34,CEACAM1,DLL4,GADD45B,IGF2,INHBB,ITGA1,LBH,MMP9,NOS2,NRCAM,SEMA3C,SERPINA3,SFRP1,SFR NOTCH1 0.794 6.89E-06 CEBPD,DLL4,ESM1,GFAP,HEYL,MCAM,NOS2,NOTCH3,PDGFB CTBP2 9.11E-06 CDH5,DLL4,LMO3,SPRY4 Growth factor APLN,ARNT2,BMP6,C1S,CD34,CD36,CD69,CEACAM1,COMP,CRIP2,CXADR,DARC,DCN,ESM1,ETS1,FBLN1,GA DD45B,GAS1 (includes EG:14451),GFAP,HLA- TGFB1 -0.118 4.42E-10 DRB1,IGF2,IL17RB,INHBB,ITGA1,MMP9,NME1(includeEG:18102),NOS2,NOTCH3,NOX4,PDGFB,SERPINA3,SFR P1,TACC2,TGFB3,THY1,TNFAIP6,TUBB4B,ZWINT FGF2 3.201 7.50E-08 ANGPT2,DCN,DLL4,ETS1,FGFR3,GFAP,IGF2,MMP9,NES,NOS2,PDGFB,PTPRE,SFRP1,SPRY4,TF VEGFA 2.843 4.47E-07 ANGPT2,CD34,CDH5,CEACAM1,DLL4,ETS1,HLX,ITGA1,MMP9,NME1 (includes EG:18102),NOS2,PDGFB ADORA2A,AKAP12,ANGPT2,CCNF,CXCR7,ESM1,ETS1,GRB14,HLX,MMP9,NES,NID2,NOS2,NRCAM,SFRP1,SO HGF 1.127 9.94E-07 X2,TNFAIP6 Chemical - endogenous ADORA2A,ARNT2,CD69,COMP,CP,CRYAA,CXADR,CXCR7,DCN,ETS1,FBLN1,FGFR3,FMO2,FMOD,GADD45B,G beta-estradiol -1.74 9.48E-11 FAP,GPC1,GPX3,HLA-DRB1,HSD11B2,IGF2,INHBB,ITGA1,KCNN2,MAL,MGST1,MMP9,MYO1B,NME1 (includes EG:18102),NOS2,NOTCH3,PDGFB,RPS4Y1,SEMA3C,SERPINA3,SFRP1,STK32B,TFAP2C,TGFB3,TNFAIP6 AKAP12,APLN,BMP6,CD34,CD36,CEACAM1,CLDN11,CP,DCN,DLL4,ETS1,FAM101B,GFAP,GFRA1,IGF2,ITGA1, tretinoin -0.413 3.17E-08 KCNJ2,LAMA4,MMP9,NES,NID2,NOS2,PDGFB,PLP1 (includes EG:18823),PTP4A3,RARRES1,RPL29 (includes EG:100039782),RPS4Y1,SFRP1,SOX7,TF,TGFB3,TNFAIP6 Chemical drug ADORA2A,ANGPT2,ATP1A2,CCNF,CD36,CD48,CD69,CDH5,CEACAM1,CEBPD,CETP,CP,CXCR7,DCN,DLL4,GA lipopolysaccharide -0.117 2.64E-07 DD45B,GAS1 (includes EG:14451),GFAP,HLA- A,INHBB,LPAR1,LYZ,MMP9,NFKBIZ,NID2,NOS2,NR1H4,PDGFB,SERPINA3,TF,THY1,TNFAIP6,TUBB4B APLN,CD36,CD69,CEACAM1,CEBPD,COL10A1,CP,CRYAA,CXADR,CXCR7,DCN,FBLN1,GADD45B,GAS1 (includes EG:14451),HLA- -1.923 2.68E-06 DRB1,HSD11B2,IGF2,IL17RB,INHBB,LAMA4,LPAR1,MMP9,NEBL,NOS2,OMD,RASD1,SERPINA3,SFRP1,TF,TGF B3,TNFAIP6 ibuprofen 1.069 7.75E-06 CD36,GFAP,MMP9,NOS2,SERPINA3 Complex PDGF BB -0.026 1.14E-08 AKAP12,BMP6,CEBPD,CP,CXCR7,DCN,ETS1,IGF2,MGST1,MMP9,NOS2,NOX4,OMD,SERPINA3,TGFB3,TRIB3 APLN,CEBPD,ESM1,GAS1 (includes Cg -0.36 4.23E-07 EG:14451),GPC1,HSD11B2,INHBB,ITGA1,MCAM,MMP9,NOS2,SFRP4,SLC4A4,TNFAIP6 Group Vegf 1.58 5.32E-07 ADORA2A,AKAP12,ANGPT2,CCNF,CDH5,CXCR7,DLL4,ESM1,ETS1,GRB14,LPAR1,MMP9,NID2,NRCAM,SFRP1 Akt 1.557 5.39E-06 CD36,CP,DLL4,ETS1,IGF2,MCAM,MMP9,NOS2,NOX4,SOX2 Cytokine PRL -1.473 9.26E-06 CD69,CEBPD,DCN,HSD11B2,IGF2,ITGA1,MGST1,NOS2,RASD1,SERPINA3 ADORA2A,AKAP12,ANGPT2,APLN,CD36,CD69,CEBPD,CHI3L2,CLDN11,CP,CXCR7,DCN,ESM1,ETS1,GADD45B, TNF 0.991 2.53E-10 GFAP,IGF2,IL17RB,LAMA4,MAN1C1,MCAM,MGST1,MMP9,NFKBIZ,NME1 (includes EG:18102),NOS2,NR1H4,PDGFB,PLP1 (includes Chemical - kinase inhibitor U0126 0.445 6.52E-06 BMP6,CD36,CD69,CDH5,CEBPD,CXCR7,ETS1,GADD45B,GFAP,IL17RB,MMP9,NOS2,SOX2,TF,TGFB3

Enzyme GNA15 5.59E-10 AKAP12,CD69,CEBPD,CP,CXCR7,MGST1,NOX4,OMD,SERPINA3,TGFB3,TRIB3 Kinase EGFR 1.749 8.55E-06 ANGPT2,GPC1,HSD11B2,IGF2,LAMA4,MMP9,NOS2,PTPRE,SERPINA3,SFRP1,TNFAIP6 Transporter APOE -1.264 4.86E-06 CD36,CETP,GPX3,MMP9,MYO1B,NOS2,NOX4,PTP4A3,SERPINA3,THY1 Other NFKBIA -1.236 3.78E-06 CD69,CEBPD,CHI3L2,CP,CXCR7,DCN,ESM1,GADD45B,GPX3,IGF2,MMP9,NOS2,SEMA3C,SEMA3F,SFRP1 WNT3A -0.05 7.30E-06 DCN,FAM101B,FMOD,GAS1 (includes EG:14451),LBH,NES,NOS2,TGFB3,THY1 Positive values of Activation z-scores indicate activation of the target genes, and negative values indicate inhibiton of the target genes. P-values were detected by Fisher's exact tests.

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