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Yano_Supplemental_Table_S4 ontology – Biological process 1 of 9

Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Total Hits Total Enrichment DLC1, CADM1, NELL2, CLSTN1, PCDHGA8, CTNNB1, NRCAM, APP, CNTNAP2, FERT2, RAPGEF1, PTPRM, MPDZ, SDK1, PCDH9, PTPRS, VEZT, NRXN1, MYH9, GO:0007155~cell CTNNA2, NCAM1, NCAM2, DDR1, LSAMP, CNTN1, 50 5.61 2.14E-08 510 311 7436 2.34 4.50E-05 4.50E-05 3.70E-05 adhesion ROR2, VCAN, DST, LIMS1, TNC, ASTN1, CTNND2, CTNND1, CDH2, NEO1, CDH4, CD24A, FAT3, PVRL3, TRO, TTYH1, MLLT4, LPP, NLGN1, PCDH19, LAMA1, ITGA9, CDH13, CDON, PSPC1 DLC1, CADM1, NELL2, CLSTN1, PCDHGA8, CTNNB1, NRCAM, APP, CNTNAP2, FERT2, RAPGEF1, PTPRM, MPDZ, SDK1, PCDH9, PTPRS, VEZT, NRXN1, MYH9, GO:0022610~biological CTNNA2, NCAM1, NCAM2, DDR1, LSAMP, CNTN1, 50 5.61 2.14E-08 510 311 7436 2.34 4.50E-05 4.50E-05 3.70E-05 adhesion ROR2, VCAN, DST, LIMS1, TNC, ASTN1, CTNND2, CTNND1, CDH2, NEO1, CDH4, CD24A, FAT3, PVRL3, TRO, TTYH1, MLLT4, LPP, NLGN1, PCDH19, LAMA1, ITGA9, CDH13, CDON, PSPC1 DCC, ENAH, PLXNA2, CAPZA2, ATP5B, ASTN1, PAX6, ZEB2, CDH2, CDH4, GLI3, CD24A, EPHB1, NRCAM, GO:0006928~cell CTTNBP2, EDNRB, APP, PTK2, ETV1, CLASP2, STRBP, 36 4.04 3.46E-07 510 205 7436 2.56 7.28E-04 3.64E-04 5.98E-04 motion NRG1, DCLK1, PLAT, SGPL1, TGFBR1, EVL, MYH9, YWHAE, NCKAP1, CTNNA2, SEMA6A, EPHA4, NDEL1, FYN, LRP6 PLXNA2, ADCY5, PAX6, GLI3, CTNNB1, LPHN2, EDNRB, LPHN3, APP, CSNK2A1, GPR45, NRG1, RAPGEF1, WWOX, SGPL1, TLE4, SPEN, NCAM1, DDR1, GRB10, GRM3, GNAQ, HIPK1, GNB1, HIPK2, PYGO1, GO:0007166~cell RNF138, ROR2, CNTN1, GNAS, PPM1L, ERBB4, surface linked 70 7.85 9.24E-07 510 564 7436 1.81 0.001944439 6.49E-04 0.001598537 ADCYAP1R1, USP9X, BMPR2, CTNND1, CD24A, EPHB1, PHIP, IGF1R, PTK2, BAI1, BAI3, AGRN, PIK3R3, AGRP, CSNK1A1, PLAT, DVL3, NLK, TGFBR1, DGKH, KCNK2, EPHA3, NTRK3, SEMA6A, EPHA4, LAMA1, ITGA9, NOTCH2, RGS20, NXN, FYN, DCP1A, CDON, GSK3B, GRLF1, LRP6, ZRANB1, CACNA1D ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, GO:0051254~positive ARID2, HNRPLL, CBFB, CTNNB1, APP, MEIS2, TCEA1, regulation of RNA 38 4.26 4.27E-06 510 247 7436 2.24 0.008947498 0.002244419 0.007381509 YAP1, AGRN, PLAGL2, ATF7IP, KLF12, SOX11, MED14, metabolic process RB1, WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, HIPK2, PBX1, RBM14, NFIA, NFIB MYO5A, SYT1, GRIK2, CAPZA2, CLSTN1, HEXB, CACNB2, CD24A, CTNNB1, NRCAM, CTTNBP2, APP, GO:0019226~transmiss 27 3.03 6.70E-06 510 148 7436 2.66 0.014018365 0.002819528 0.011594273 PTK2, DMD, AGRN, PPP3CA, NRG1, SCD2, NRXN3, ion of nerve impulse NF1, NLGN1, NRXN1, QK, CTNNA2, GRM3, FYN, CACNA1C ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, GO:0045893~positive NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, regulation of ARID2, CBFB, CTNNB1, APP, MEIS2, TCEA1, YAP1, 37 4.15 9.01E-06 510 245 7436 2.20 0.018790947 0.003156631 0.015578904 transcription, DNA- AGRN, PLAGL2, ATF7IP, KLF12, SOX11, MED14, RB1, dependent WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, HIPK2, PBX1, RBM14, NFIA, NFIB ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, CTCF, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, GO:0010628~positive 9430076C15RIK, GLI3, ARID2, CBFB, CTNNB1, APP, regulation of gene 41 4.60 1.25E-05 510 289 7436 2.07 0.025921746 0.003744918 0.021568372 MEIS2, ETV1, TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, expression KLF12, SOX11, MED14, RB1, WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, DCP1A, HIPK2, PBX1, RBM14, NFIA, NFIB MYO5A, ADCY3, SYT1, GRIK2, CAPZA2, ADCY5, HEXB, CLSTN1, CTNND2, CACNB2, RORB, GRIN3A, CD24A, GO:0050877~neurologi CTNNB1, NRCAM, CTTNBP2, APP, PTK2, PDE1C, DMD, 40 4.48 1.27E-05 510 279 7436 2.09 0.026415026 0.003340679 0.021984306 cal system process PTN, PPP3CA, AGRN, NRG1, TUB, SCD2, RPGR, NRXN3, NF1, NLGN1, NRXN1, QK, CTNNA2, GRM3, FYN, GNB1, CACNA1C, PBX3, CACNA1D, FBXO11 DCC, ENAH, LIMS1, SHROOM3, PAX6, SOX6, CDH4, GLI3, EPHB1, CTNNB1, NRCAM, APP, PTK2, DMD, GO:0000902~cell 32 3.59 1.76E-05 510 203 7436 2.30 0.036326858 0.004103016 0.030386561 NUMB, ETV1, CLASP2, NRG1, DCLK1, DSCAM, morphogenesis CSNK1A1, PTPRZ1, TBCE, EVL, MYH9, WWTR1, CTNNA2, SEMA6A, LAMA1, EPHA4, NDEL1, DST ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, GO:0045935~positive NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, regulation of GLI3, ARID2, HNRPLL, CBFB, CTNNB1, APP, MEIS2, nucleobase, nucleoside, 42 4.71 1.97E-05 510 305 7436 2.01 0.040546096 0.004130546 0.033989246 ETV1, TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, KLF12, nucleotide and nucleic SOX11, MED14, RB1, WWTR1, NCOA2, CSRNP3, acid metabolic process ZFP462, ETS1, DCP1A, HIPK2, BRE, PBX1, RBM14, NFIA, NFIB GO:0045944~positive HMGB2, CNBP, PAX6, SOX5, CASK, SOX6, ZEB1, regulation of RORA, CNOT7, ARID2, CBFB, CTNNB1, APP, MEIS2, transcription from 32 3.59 2.14E-05 510 205 7436 2.28 0.044143192 0.004095876 0.037073132 TCEA1, AGRN, YAP1, PLAGL2, KLF12, SOX11, MED14, RNA polymerase II RB1, WWTR1, NCOA2, ZFP462, CSRNP3, ETS1, HIPK2, promoter PBX1, RBM14, NFIA, NFIB Yano_Supplemental_Table_S4 – Biological process 2 of 9

Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, GO:0045941~positive GLI3, ARID2, CBFB, CTNNB1, APP, MEIS2, ETV1, regulation of 40 4.48 2.28E-05 510 286 7436 2.04 0.046838229 0.003989574 0.03939121 TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, KLF12, SOX11, transcription MED14, RB1, WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, DCP1A, HIPK2, PBX1, RBM14, NFIA, NFIB LIMS1, CADM1, CLSTN1, ASTN1, PCDHGA8, NLGN1, GO:0016337~cell-cell CTNND1, PCDH9, VEZT, CDH2, MYH9, CDH4, CD24A, 25 2.80 2.31E-05 510 140 7436 2.60 0.047566658 0.00374184 0.040018869 adhesion PCDH19, CTNNB1, CTNNA2, NRCAM, NCAM1, CDH13, FAT3, PVRL3, CDON, TTYH1, ROR2, RAPGEF1 DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, CDH4, GLI3, GO:0048812~neuron EPHB1, CTNNA2, NRCAM, SEMA6A, EPHA4, APP, projection 22 2.47 2.83E-05 510 115 7436 2.79 0.057817626 0.004244994 0.048902575 PTK2, NDEL1, DMD, NUMB, ETV1, DST, DCLK1, morphogenesis DSCAM PLAT, DCC, SGPL1, PLXNA2, CAPZA2, ATP5B, GO:0016477~cell TGFBR1, ASTN1, PAX6, ZEB2, CDH2, MYH9, YWHAE, 25 2.80 2.95E-05 510 142 7436 2.57 0.060209955 0.004131361 0.050989614 migration CD24A, NCKAP1, CTNNA2, CTTNBP2, EDNRB, PTK2, NDEL1, FYN, LRP6, CLASP2, NRG1, DCLK1 ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, GO:0051173~positive GLI3, ARID2, HNRPLL, CBFB, CTNNB1, APP, MEIS2, regulation of nitrogen 42 4.71 3.40E-05 510 312 7436 1.96 0.069173172 0.004470106 0.058856143 ETV1, TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, KLF12, compound metabolic SOX11, MED14, RB1, WWTR1, NCOA2, CSRNP3, process ZFP462, ETS1, DCP1A, HIPK2, BRE, PBX1, RBM14, NFIA, NFIB CAPZA2, ATP5B, CASK, EIF2A, D8ERTD82E, CTTNBP2, APP, CSNK2A1, SLK, PAK2, PAK3, FERT2, TLK1, BRD4, AKT3, PTPRK, PAN3, PTPRM, ROCK1, PTPRG, WNK1, PI4KA, CDK8, PTPRS, PTPRT, MARK3, PRKCE, MARK1, MAP4K3, ATP6V1A, MAP4K4, DDR1, GO:0006793~phosphor 68 7.62 3.60E-05 510 603 7436 1.64 0.072975671 0.004447461 0.062216111 EIF2AK1, HIPK1, HIPK2, ROR2, MAPK8, PPM1L, us metabolic process CAMK1D, ERBB4, SSH2, BMPR2, ABI1, EPHB1, IGF1R, PTK2, TTBK2, PPP2CA, PPP1R12A, TNKS, PPP3CA, DCLK1, GPD2, CSNK1A1, PTPRD, TAOK1, PTPRZ1, NLK, TGFBR1, MAP2K4, EPHA3, NTRK3, EPHA4, ICK, FYN, ATP6V1E1, RSRC1, GSK3B CAPZA2, ATP5B, CASK, EIF2A, D8ERTD82E, CTTNBP2, APP, CSNK2A1, SLK, PAK2, PAK3, FERT2, TLK1, BRD4, AKT3, PTPRK, PAN3, PTPRM, ROCK1, PTPRG, WNK1, PI4KA, CDK8, PTPRS, PTPRT, MARK3, PRKCE, MARK1, MAP4K3, ATP6V1A, MAP4K4, DDR1, GO:0006796~phosphat 68 7.62 3.60E-05 510 603 7436 1.64 0.072975671 0.004447461 0.062216111 EIF2AK1, HIPK1, HIPK2, ROR2, MAPK8, PPM1L, e metabolic process CAMK1D, ERBB4, SSH2, BMPR2, ABI1, EPHB1, IGF1R, PTK2, TTBK2, PPP2CA, PPP1R12A, TNKS, PPP3CA, DCLK1, GPD2, CSNK1A1, PTPRD, TAOK1, PTPRZ1, NLK, TGFBR1, MAP2K4, EPHA3, NTRK3, EPHA4, ICK, FYN, ATP6V1E1, RSRC1, GSK3B MYO5A, SYT1, GRIK2, NRXN3, CAPZA2, CLSTN1, GO:0007268~synaptic NLGN1, CACNB2, NRXN1, CD24A, CTNNB1, CTNNA2, 21 2.35 6.09E-05 510 112 7436 2.73 0.120391176 0.007101221 0.10530106 transmission CTTNBP2, APP, PTK2, GRM3, DMD, AGRN, PPP3CA, CACNA1C, NRG1 DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, CDH4, GLI3, GO:0007409~axonogen 20 2.24 7.70E-05 510 105 7436 2.78 0.149620401 0.00849385 0.133023852 EPHB1, CTNNA2, NRCAM, SEMA6A, EPHA4, APP, esis PTK2, NDEL1, NUMB, ETV1, DST, DCLK1 GO:0000904~cell DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, MYH9, CDH4, morphogenesis GLI3, EPHB1, CTNNB1, CTNNA2, NRCAM, SEMA6A, 23 2.58 8.80E-05 510 133 7436 2.52 0.169196272 0.009225269 0.15212438 involved in EPHA4, APP, PTK2, NDEL1, NUMB, ETV1, DST, DCLK1, differentiation DSCAM PLAT, DCC, SGPL1, PLXNA2, CAPZA2, ATP5B, GO:0048870~cell TGFBR1, ASTN1, PAX6, ZEB2, CDH2, MYH9, YWHAE, 25 2.80 9.13E-05 510 152 7436 2.40 0.174893647 0.009112654 0.157767323 motility CD24A, NCKAP1, CTNNA2, CTTNBP2, EDNRB, PTK2, NDEL1, FYN, LRP6, CLASP2, NRG1, DCLK1 PLAT, DCC, SGPL1, PLXNA2, CAPZA2, ATP5B, GO:0051674~localizati TGFBR1, ASTN1, PAX6, ZEB2, CDH2, MYH9, YWHAE, 25 2.80 9.13E-05 510 152 7436 2.40 0.174893647 0.009112654 0.157767323 on of cell CD24A, NCKAP1, CTNNA2, CTTNBP2, EDNRB, PTK2, NDEL1, FYN, LRP6, CLASP2, NRG1, DCLK1 DCC, ENAH, PAX6, RORB, GRIN3A, CDH4, GLI3, GO:0048666~neuron CD24A, EPHB1, NRCAM, APP, PTK2, DMD, NUMB, 28 3.14 1.02E-04 510 182 7436 2.24 0.192801733 0.009688487 0.175759342 development ETV1, DCLK1, DSCAM, RPGR, PTPRZ1, TBCE, EVL, CTNNA2, SEMA6A, EPHA4, NDEL1, GNAQ, PBX3, DST ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, GO:0031328~positive GLI3, ARID2, CBFB, CTNNB1, APP, MEIS2, NPM1, regulation of cellular 41 4.60 1.06E-04 510 317 7436 1.89 0.200399605 0.009676495 0.183512743 ETV1, TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, KLF12, biosynthetic process SOX11, MED14, RB1, WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, DCP1A, HIPK2, PBX1, RBM14, NFIA, NFIB Yano_Supplemental_Table_S4 Gene ontology – Biological process 3 of 9

List Pop Pop Fold GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0048667~cell DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, CDH4, GLI3, morphogenesis 21 2.35 1.15E-04 510 117 7436 2.62 0.214752315 0.009623637 0.198360727 EPHB1, CTNNA2, NRCAM, SEMA6A, EPHA4, APP, PTK2, involved in neuron NDEL1, NUMB, ETV1, DST, DCLK1, DSCAM differentiation DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, GRIN3A, GO:0031175~neuron CDH4, GLI3, CD24A, EPHB1, CTNNA2, NRCAM, 24 2.69 1.19E-04 510 145 7436 2.41 0.221078392 0.009563395 0.20499076 projection development SEMA6A, EPHA4, APP, PTK2, NDEL1, DMD, NUMB, ETV1, DST, DCLK1, DSCAM DCC, ENAH, LIMS1, SHROOM3, PAX6, SOX6, CDH4, GO:0032989~cellular GLI3, EPHB1, CTNNB1, NRCAM, APP, PTK2, DMD, component 32 3.59 1.31E-04 510 225 7436 2.07 0.241234408 0.01017244 0.226477127 NUMB, ETV1, CLASP2, NRG1, DCLK1, DSCAM, morphogenesis CSNK1A1, PTPRZ1, TBCE, EVL, MYH9, WWTR1, CTNNA2, SEMA6A, LAMA1, EPHA4, NDEL1, DST CAPZA2, CASK, EIF2A, D8ERTD82E, CTTNBP2, APP, CSNK2A1, PAK2, SLK, PAK3, TLK1, FERT2, BRD4, AKT3, PAN3, ROCK1, CDK8, WNK1, PRKCE, MARK3, GO:0006468~ MARK1, MAP4K3, DDR1, MAP4K4, EIF2AK1, HIPK1, amino acid 51 5.72 1.31E-04 510 431 7436 1.73 0.241521191 0.009824295 0.226786906 HIPK2, ROR2, MAPK8, CAMK1D, ERBB4, BMPR2, ABI1, phosphorylation EPHB1, IGF1R, PTK2, TTBK2, TNKS, DCLK1, CSNK1A1, TAOK1, TGFBR1, NLK, MAP2K4, EPHA3, NTRK3, EPHA4, ICK, FYN, RSRC1, GSK3B ENY2, HMGB2, CNBP, SOX5, PAX6, CASK, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, 9430076C15RIK, GO:0009891~positive GLI3, ARID2, CBFB, CTNNB1, APP, MEIS2, NPM1, ETV1, regulation of 41 4.60 1.33E-04 510 320 7436 1.87 0.243602021 0.009580966 0.229038074 TCEA1, YAP1, AGRN, PLAGL2, ATF7IP, KLF12, SOX11, biosynthetic process MED14, RB1, WWTR1, NCOA2, CSRNP3, ZFP462, ETS1, DCP1A, HIPK2, PBX1, RBM14, NFIA, NFIB DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, WWTR1, CDH4, GO:0048858~cell GLI3, EPHB1, CTNNA2, NRCAM, SEMA6A, EPHA4, APP, projection 23 2.58 1.38E-04 510 137 7436 2.45 0.252434018 0.009650885 0.238661928 PTK2, NDEL1, DMD, NUMB, ETV1, DST, DCLK1, morphogenesis DSCAM ENY2, HMGB2, CNBP, SOX5, BMPR2, PAX6, CASK, CTCF, RORB, NFYB, SOX6, ZEB1, RORA, CNOT7, GO:0010604~positive 9430076C15RIK, GLI3, CD24A, ARID2, HNRPLL, CBFB, regulation of 46 5.16 1.40E-04 510 376 7436 1.78 0.255673729 0.009479807 0.242220399 CTNNB1, APP, MEIS2, ETV1, TCEA1, YAP1, AGRN, macromolecule PLAGL2, ATF7IP, KLF12, SOX11, MED14, RB1, WWTR1, metabolic process NCOA2, CSRNP3, ZFP462, NEDD4, ETS1, DCP1A, HIPK2, BRE, PBX1, RBM14, NFIA, NFIB GO:0050808~synapse MYO5A, APP, CADM1, NRXN3, TNC, NLGN1, NRXN1, 11 1.23 2.15E-04 510 39 7436 4.11 0.364271072 0.014055998 0.371350196 organization CDH2, AGRN, NRG1, CTNNB1 DCC, ENAH, SOX5, PAX6, RORB, GRIN3A, RORA, CDH4, GLI3, CD24A, EPHB1, NRCAM, APP, PTK2, DMD, NUMB, GO:0030182~neuron 33 3.70 2.22E-04 510 242 7436 1.99 0.374119846 0.014099547 0.384125227 ETV1, NRG1, DCLK1, DSCAM, RPGR, PTPRZ1, TGFBR1, differentiation TBCE, EVL, CTNNA2, NTRK3, SEMA6A, EPHA4, NDEL1, GNAQ, PBX3, DST CAPZA2, ATP5B, CASK, EIF2A, D8ERTD82E, CTTNBP2, APP, CSNK2A1, PAK2, SLK, PAK3, TLK1, FERT2, BRD4, AKT3, PAN3, ROCK1, CDK8, PI4KA, WNK1, MARK3, PRKCE, MARK1, MAP4K3, ATP6V1A, MAP4K4, DDR1, GO:0016310~phosphor 55 6.17 2.73E-04 510 490 7436 1.64 0.436903189 0.016749428 0.470573144 EIF2AK1, HIPK1, HIPK2, ROR2, MAPK8, CAMK1D, ylation ERBB4, BMPR2, ABI1, EPHB1, IGF1R, PTK2, TTBK2, TNKS, DCLK1, CSNK1A1, TAOK1, NLK, TGFBR1, MAP2K4, EPHA3, NTRK3, EPHA4, ICK, FYN, ATP6V1E1, RSRC1, GSK3B GO:0007416~synaptoge 7 0.78 2.93E-04 510 15 7436 6.80 0.460781288 0.017491895 0.505987174 APP, CADM1, NRXN3, NLGN1, NRXN1, CDH2, NRG1 nesis DCC, ENAH, PTPRZ1, PAX6, TBCE, EVL, WWTR1, CDH4, GO:0032990~cell part GLI3, EPHB1, CTNNA2, NRCAM, SEMA6A, EPHA4, APP, 23 2.58 3.88E-04 510 147 7436 2.28 0.558607353 0.022461141 0.669436811 morphogenesis PTK2, NDEL1, DMD, NUMB, ETV1, DST, DCLK1, DSCAM DCC, ENAH, PAX6, GRIN3A, CDH4, GLI3, CD24A, EPHB1, NRCAM, APP, PTK2, DMD, NUMB, TTYH1, GO:0030030~cell 29 3.25 8.68E-04 510 218 7436 1.94 0.8392447 0.048201517 1.490044604 ETV1, DCLK1, DSCAM, ROCK1, PTPRZ1, TBCE, EVL, projection organization MYH9, WWTR1, CTNNA2, NCKAP1, SEMA6A, EPHA4, NDEL1, DST MYO5A, SYT1, GRIK2, NRXN3, TNC, CAPZA2, CLSTN1, GO:0007267~cell-cell NLGN1, CACNB2, NRXN1, RIMS2, CD24A, CTNNB1, 23 2.58 8.89E-04 510 156 7436 2.15 0.846385942 0.048102276 1.526802165 signaling CTNNA2, CTTNBP2, APP, PTK2, GRM3, DMD, AGRN, PPP3CA, CACNA1C, NRG1 HMGB2, CNBP, SOX5, PAX6, CASK, SOX6, ZEB1, RORA, CNOT7, ARID2, CBFB, CTNNB1, APP, MEIS2, GO:0006357~regulation TCEA1, YAP1, AGRN, TCF4, PLAGL2, ATF7IP, KLF12, of transcription from 44 4.93 9.20E-04 510 386 7436 1.66 0.856074336 0.048489027 1.579476806 JARID2, SOX11, TLE4, MED14, RB1, SPEN, WWTR1, RNA polymerase II MED13L, HLTF, FOXP1, NCOA2, CSRNP3, ZFP462, promoter HIPK1, ETS1, HIPK2, PBX1, HIVEP1, MDM4, RBM14, TCF12, NFIA, NFIB GO:0048592~eye RPGR, PVRL3, NF1, LRP6, PAX6, RORB, ZEB1, GLI3, 11 1.23 0.001067141 510 47 7436 3.41 0.894453104 0.054664131 1.829858178 morphogenesis EPHB1, CTNNB1, DSCAM GO:0009952~anterior/ TGFBR1, PAX6, BMPR2, ABI1, ZEB2, GLI3, NCKAP1, posterior pattern 13 1.46 0.00151935 510 66 7436 2.87 0.959326756 0.075129978 2.595716738 CTNNB1, HIPK1, HIPK2, LRP6, ROR2, PBX1 formation Yano_Supplemental_Table_S4 Gene ontology – Biological process 4 of 9

List Pop Pop Fold GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0043062~extracellul MYO5A, CADM1, NRXN3, TGFBR1, TNC, NF1, ar structure 16 1.79 0.001663945 510 94 7436 2.48 0.970018832 0.080112984 2.839410768 HSD17B12, NLGN1, CDH2, NRXN1, CTNNB1, APP, PTK2, organization SMOC1, AGRN, NRG1 GO:0046777~protein CTTNBP2, IGF1R, PTK2, EIF2AK1, CSNK2A1, PAK2, amino acid 11 1.23 0.002057406 510 51 7436 3.14 0.986929003 0.095948387 3.499630823 FYN, NLK, TGFBR1, CAPZA2, FERT2 autophosphorylation GO:0007411~axon DCC, NRCAM, SEMA6A, EPHA4, APP, ENAH, PAX6, 12 1.35 0.002528381 510 61 7436 2.87 0.995163255 0.114117325 4.284360564 guidance ETV1, EVL, CDH4, GLI3, EPHB1 DLC1, ENAH, SHROOM3, TNC, CTNND1, ZEB2, GLI3, GO:0002009~morphoge 17 1.91 0.002609181 510 108 7436 2.30 0.995921868 0.115089927 4.418382081 SHANK3, CTNNB1, ZIC2, NCKAP1, DDR1, IGF1R, nesis of an epithelium LAMA1, NOTCH2, GRLF1, PBX1 GO:0016055~Wnt CSNK1A1, DVL3, NLK, CTNND1, TLE4, CTNNB1, receptor signaling 15 1.68 0.003685334 510 92 7436 2.38 0.999580166 0.155521388 6.18660364 CSNK2A1, NXN, GSK3B, LRP6, PYGO1, ROR2, ZRANB1, pathway RNF138, WWOX PLAT, SGPL1, ERBB4, NLK, TGFBR1, USP9X, BMPR2, GO:0007167~ EPHB1, EPHA3, PHIP, NTRK3, DDR1, IGF1R, EPHA4, linked receptor protein 23 2.58 0.004509287 510 177 7436 1.89 0.999926486 0.183322785 7.519554592 GRB10, PTK2, DCP1A, HIPK2, ROR2, PPM1L, AGRN, signaling pathway PIK3R3, RAPGEF1 DLC1, ENAH, IMPAD1, SHROOM3, TGFBR1, FTO, GO:0048598~embryonic BMPR2, ZEB2, ZEB1, GLI3, SHANK3, CTNNB1, NCKAP1, 24 2.69 0.00485401 510 189 7436 1.85 0.999964552 0.192238335 8.071919307 morphogenesis ZIC2, NOTCH2, GNAQ, CDON, LRP6, GRLF1, ROR2, PBX1, GNAS, FBN2, PPAP2B MYO5A, GRIK2, ADCY5, NF1, HEXB, ASTN1, CTNND2, TBCE, PRKCE, PLCL1, EPHA4, APP, NPAS3, GNAQ, GO:0007610~behavior 24 2.69 0.00485401 510 189 7436 1.85 0.999964552 0.192238335 8.071919307 HIPK2, PTN, ETV1, FERT2, STRBP, NRG1, CACNA1C, PBX3, AGRP, DSCAM GO:0048593~camera- PVRL3, NF1, LRP6, ZEB1, GLI3, EPHB1, CTNNB1, type eye 8 0.90 0.005060621 510 32 7436 3.65 0.999977108 0.195919285 8.401489369 DSCAM morphogenesis GO:0035107~appendag NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, 11 1.23 0.00618845 510 59 7436 2.72 0.9999979 0.230079033 10.18098236 e morphogenesis FBN2, ASPH, GLI3, CTNNB1 GO:0035108~limb NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, 11 1.23 0.00618845 510 59 7436 2.72 0.9999979 0.230079033 10.18098236 morphogenesis FBN2, ASPH, GLI3, CTNNB1 SHROOM3, TGFBR1, FTO, PAX6, BMPR2, ZEB2, ABI1, GO:0007389~pattern 19 2.13 0.006381843 510 139 7436 1.99 0.999998606 0.232316003 10.48282724 ZEB1, GLI3, CTNNB1, RTTN, NCKAP1, NOTCH2, HIPK1, specification process HIPK2, LRP6, ROR2, PBX1, ASPH DLC1, ENAH, SHROOM3, TNC, BMPR2, CTNND1, ZEB2, GO:0048729~tissue 19 2.13 0.006381843 510 139 7436 1.99 0.999998606 0.232316003 10.48282724 GLI3, TPM1, SHANK3, CTNNB1, ZIC2, NCKAP1, DDR1, morphogenesis IGF1R, LAMA1, NOTCH2, GRLF1, PBX1 GO:0008285~negative DLC1, PDS5B, JARID2, CAPZA2, NF1, PAX6, RB1, ZEB1, regulation of cell 19 2.13 0.006381843 510 139 7436 1.99 0.999998606 0.232316003 10.48282724 GLI3, CD24A, DDR1, CTTNBP2, NOTCH2, EIF2AK1, proliferation NPM1, MYO16, ASPH, SMARCA2, NFIB BCAT2, TGFBR1, CAPZA2, TNC, NF1, PAX6, CTNND1, GO:0048732~gland 15 1.68 0.006551001 510 98 7436 2.23 0.999999026 0.233705242 10.74606198 GLI3, CTNNB1, DDR1, IGF1R, LAMA1, CTTNBP2, development ARHGAP5, PBX1 GO:0042692~muscle APP, CDON, TNC, NEO1, PPP3CA, RB1, AGRN, SOX6, 12 1.35 0.006726363 510 69 7436 2.54 0.999999328 0.235230433 11.01818291 cell differentiation MYH9, NRG1, FOXP1, QK GO:0001508~regulation MYO5A, SCD2, GNAQ, GRIK2, FYN, NF1, HEXB, NRG1, 9 1.01 0.006788706 510 42 7436 3.12 0.999999412 0.233302012 11.11473564 of action potential QK GO:0048736~appendag NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, 11 1.23 0.006985141 510 60 7436 2.67 0.999999612 0.235402662 11.41831749 e development FBN2, ASPH, GLI3, CTNNB1 GO:0060173~limb NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, 11 1.23 0.006985141 510 60 7436 2.67 0.999999612 0.235402662 11.41831749 development FBN2, ASPH, GLI3, CTNNB1 SGPL1, IMPAD1, TGFBR1, NF1, HEXB, SOX5, ZEB1, GO:0001501~skeletal 19 2.13 0.007395306 510 141 7436 1.96 0.999999837 0.243573425 12.04906132 SOX6, WWTR1, GLI3, CBFB, CTNNB1, GNAQ, ROR2, system development PTN, MAPK8, PBX1, GNAS, WWOX GO:0030326~embryonic NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, 10 1.12 0.008018495 510 52 7436 2.80 0.999999957 0.25729508 12.99929654 limb morphogenesis FBN2, GLI3, CTNNB1 GO:0035113~embryonic NOTCH2, IMPAD1, GNAQ, FTO, LRP6, GNAS, PBX1, appendage 10 1.12 0.008018495 510 52 7436 2.80 0.999999957 0.25729508 12.99929654 FBN2, GLI3, CTNNB1 morphogenesis MYO5A, DLC1, ENAH, SHROOM3, ROCK1, CAPZA2, NF1, GO:0030029~ 18 2.02 0.008348415 510 132 7436 1.99 0.999999979 0.262438824 13.49843235 RHOQ, EVL, MYH9, NCKAP1, CTTNBP2, FMN2, filament-based process EPB4.1L3, TMSB4X, ARHGAP8, DIAP2, DIAP3 DLC1, ENAH, SHROOM3, CAPZA2, RHOQ, HOOK3, CTTNBP2, PTK2, NPM1, ARHGAP8, PSTPIP2, ROCK1, GO:0007010~cytoskele 27 3.03 0.008463422 510 232 7436 1.70 0.999999983 0.261686547 13.67179265 NF1, TBCE, EVL, MYH9, MARK1, NCKAP1, EPB4.1L3, ton organization FMN2, NDEL1, CNTROB, TMSB4X, DIAP2, DST, DIAP3, ARHGAP10 GO:0019228~regulation of action potential in 8 0.90 0.00846372 510 35 7436 3.33 0.999999983 0.257951655 13.6722401 MYO5A, SCD2, GRIK2, FYN, NF1, HEXB, NRG1, QK neuron GO:0051640~organelle MYO5A, SEMA6A, FMN2, PTK2, NDEL1, PLXNA2, NPM1, 9 1.01 0.009041456 510 44 7436 2.98 0.999999995 0.269168442 14.53816131 localization NLGN1, MYH9 GO:0051146~striated APP, CDON, TNC, NEO1, PPP3CA, RB1, AGRN, MYH9, muscle cell 10 1.12 0.009090847 510 53 7436 2.75 0.999999996 0.266705366 14.61180824 NRG1, FOXP1 differentiation Yano_Supplemental_Table_S4 Gene ontology – Biological process 5 of 9

List Pop Pop Fold GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0030036~actin DLC1, ENAH, SHROOM3, ROCK1, CAPZA2, NF1, RHOQ, 17 1.91 0.009411282 510 123 7436 2.02 0.999999998 0.271010174 15.08816122 EVL, MYH9, NCKAP1, CTTNBP2, FMN2, EPB4.1L3, organization TMSB4X, ARHGAP8, DIAP2, DIAP3 GO:0007169~transmem PLAT, SGPL1, ERBB4, BMPR2, EPHB1, EPHA3, NTRK3, brane receptor protein 17 1.91 0.009411282 510 123 7436 2.02 0.999999998 0.271010174 15.08816122 PHIP, DDR1, IGF1R, EPHA4, GRB10, PTK2, ROR2, AGRN, PIK3R3, RAPGEF1 signaling pathway GO:0045762~positive regulation of adenylate 5 0.56 0.009433873 510 13 7436 5.61 0.999999998 0.267950357 15.12164898 ADCY3, GNAQ, ADCY5, NF1, GNAS cyclase activity GO:0031281~positive regulation of cyclase 5 0.56 0.009433873 510 13 7436 5.61 0.999999998 0.267950357 15.12164898 ADCY3, GNAQ, ADCY5, NF1, GNAS activity GO:0021955~central nervous system 5 0.56 0.009433873 510 13 7436 5.61 0.999999998 0.267950357 15.12164898 DCC, PTK2, NDEL1, EPHB1, DCLK1 neuron axonogenesis GO:0051349~positive regulation of 5 0.56 0.009433873 510 13 7436 5.61 0.999999998 0.267950357 15.12164898 ADCY3, GNAQ, ADCY5, NF1, GNAS activity GO:0001654~eye RPGR, MEIS2, PVRL3, NF1, GRLF1, LRP6, PAX6, RORB, 13 1.46 0.009454358 510 82 7436 2.31 0.999999998 0.26492182 15.15200474 development ZEB1, GLI3, EPHB1, CTNNB1, DSCAM GO:0060562~epithelial DLC1, DDR1, LAMA1, ENAH, SHROOM3, GRLF1, PBX1, 12 1.35 0.011332626 510 74 7436 2.36 1 0.304885318 17.89228702 tube morphogenesis ZEB2, GLI3, SHANK3, NCKAP1, ZIC2 GO:0009791~post- SGPL1, IMPAD1, GNAQ, TGFBR1, PYGO1, TBCE, GNAS, embryonic 10 1.12 0.011556916 510 55 7436 2.65 1 0.306068546 18.21388173 SOX6, ITPR1, DSCAM development GO:0001764~neuron DCC, CTTNBP2, PTK2, NDEL1, FYN, CAPZA2, PAX6, 9 1.01 0.011809706 510 46 7436 2.85 1 0.307834657 18.57491716 migration YWHAE, DCLK1 GO:0021953~central nervous system 7 0.78 0.01226169 510 29 7436 3.52 1 0.313783074 19.21670341 DCC, PTK2, NDEL1, GNAQ, SOX5, EPHB1, DCLK1 neuron differentiation GO:0006874~cellular APP, ATP2A2, GNB1, GRIK2, CLSTN1, HEXB, calcium ion 9 1.01 0.015156082 510 48 7436 2.73 1 0.368383156 23.21491892 CACNA1C, CD24A, ITPR1 homeostasis DLC1, ENAH, SHROOM3, TNC, PAX6, CTNND1, ZEB2, GO:0060429~epithelium 19 2.13 0.015527275 510 152 7436 1.82 1 0.371351336 23.71396796 GLI3, SHANK3, CTNNB1, ZIC2, NCKAP1, DDR1, IGF1R, development LAMA1, NOTCH2, GRLF1, PBX1, VEZF1 GO:0010171~body 5 0.56 0.016147819 510 15 7436 4.86 1 0.378847572 24.5414387 SGPL1, CDON, GNAS, ASPH, NCKAP1 morphogenesis GO:0060606~tube 7 0.78 0.016930013 510 31 7436 3.29 1 0.388964982 25.57241665 DLC1, ENAH, SHROOM3, GRLF1, ZEB2, NCKAP1, ZIC2 closure GO:0042552~myelinatio 7 0.78 0.016930013 510 31 7436 3.29 1 0.388964982 25.57241665 MYO5A, SCD2, FYN, NF1, HEXB, NRG1, QK n GO:0001843~neural 7 0.78 0.016930013 510 31 7436 3.29 1 0.388964982 25.57241665 DLC1, ENAH, SHROOM3, GRLF1, ZEB2, NCKAP1, ZIC2 tube closure GO:0043473~pigmentat 7 0.78 0.016930013 510 31 7436 3.29 1 0.388964982 25.57241665 MYO5A, EDNRB, SHROOM3, GNAQ, NF1, DOCK7, ZIC2 ion GO:0001838~embryoni DLC1, ENAH, SHROOM3, GRLF1, ZEB2, SHANK3, c epithelial tube 8 0.90 0.017475292 510 40 7436 2.92 1 0.394520286 26.28326073 NCKAP1, ZIC2 formation GO:0030111~regulation of Wnt receptor 6 0.67 0.01769707 510 23 7436 3.80 1 0.394307859 26.57054419 NLK, LRP6, ZRANB1, ZEB2, PPAP2B, WWOX signaling pathway GO:0055074~calcium APP, ATP2A2, GNB1, GRIK2, CLSTN1, HEXB, 9 1.01 0.019141402 510 50 7436 2.62 1 0.414658899 28.41583203 ion homeostasis CACNA1C, CD24A, ITPR1 GO:0014020~primary 7 0.78 0.019669103 510 32 7436 3.19 1 0.41918546 29.0790612 DLC1, ENAH, SHROOM3, GRLF1, ZEB2, NCKAP1, ZIC2 neural tube formation GO:0021954~central nervous system 6 0.67 0.021131379 510 24 7436 3.65 1 0.438229432 30.88676959 DCC, PTK2, NDEL1, GNAQ, EPHB1, DCLK1 neuron development MYO5A, ADCY3, TUB, RPGR, NF1, HEXB, CTNND2, GO:0050890~cognition 18 2.02 0.021353215 510 146 7436 1.80 1 0.437522614 31.15718735 CACNB2, RORB, APP, GRM3, GNB1, PDE1C, FYN, PTN, CACNA1C, CACNA1D, FBXO11 GO:0035148~tube DLC1, ENAH, SHROOM3, GRLF1, ZEB2, SHANK3, 8 0.90 0.022488221 510 42 7436 2.78 1 0.450507677 32.52522844 lumen formation NCKAP1, ZIC2 GO:0007272~ensheath 7 0.78 0.022694889 510 33 7436 3.09 1 0.449465655 32.77155555 MYO5A, SCD2, FYN, NF1, HEXB, NRG1, QK ment of neurons GO:0008366~axon 7 0.78 0.022694889 510 33 7436 3.09 1 0.449465655 32.77155555 MYO5A, SCD2, FYN, NF1, HEXB, NRG1, QK ensheathment GO:0021915~neural DLC1, ENAH, SHROOM3, NF1, GRLF1, PAX6, ZEB2, 10 1.12 0.024188108 510 62 7436 2.35 1 0.466799571 34.52630691 tube development GLI3, NCKAP1, ZIC2 GO:0009950~dorsal/ve 3 0.34 0.025574998 510 4 7436 10.94 1 0.481787278 36.11737275 LRP6, PAX6, CTNNB1 ntral axis specification GO:0051642~centroso 3 0.34 0.025574998 510 4 7436 10.94 1 0.481787278 36.11737275 SEMA6A, NDEL1, PLXNA2 me localization Yano_Supplemental_Table_S4 Gene ontology – Biological process 6 of 9

Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment MYO5A, ADCY5, HEXB, TBCE, ASTN1, EPHA4, APP, GO:0007626~locomoto 14 1.57 0.026397132 510 105 7436 1.94 1 0.488652377 37.04326789 NPAS3, HIPK2, FERT2, PBX3, NRG1, CACNA1C, ry behavior DSCAM GO:0006875~cellular APP, ATP2A2, GNB1, GRIK2, CLSTN1, HEXB, 9 1.01 0.026442491 510 53 7436 2.48 1 0.485196149 37.0939819 metal ion homeostasis CACNA1C, CD24A, ITPR1 GO:0016331~morphoge DLC1, ENAH, SHROOM3, GRLF1, ZEB2, SHANK3, nesis of embryonic 9 1.01 0.026442491 510 53 7436 2.48 1 0.485196149 37.0939819 NCKAP1, CTNNB1, ZIC2 epithelium GO:0007600~sensory MYO5A, ADCY3, TUB, GRM3, RPGR, FYN, PDE1C, 13 1.46 0.028000808 510 95 7436 2.00 1 0.501163679 38.81307282 perception GNB1, HEXB, CACNB2, RORB, CACNA1D, FBXO11 MYO5A, SCD2, GRIK2, NF1, HEXB, CLSTN1, CD24A, GO:0006873~cellular 18 2.02 0.031957986 510 153 7436 1.72 1 0.544443218 42.98175997 KCNK2, ITPR1, QK, APP, GNAQ, ATP2A2, GNB1, FYN, ion homeostasis PPP3CA, NRG1, CACNA1C GO:0055065~metal ion APP, ATP2A2, GNB1, GRIK2, CLSTN1, HEXB, 9 1.01 0.0322679 510 55 7436 2.39 1 0.543863564 43.29667712 homeostasis CACNA1C, CD24A, ITPR1 LMO3, MORF4L2, CASK, CNOT2, CBX3, RORB, RORA, CNOT7, CBFB, CTNNB1, CNOT4, ESF1, APP, ZFP93, CASP8AP2, ZFP687, ZFP273, MED14, ZFP462, PIAS2, SMARCA2, HMGB2, CNBP, TSHZ2, SOX5, SOX6, ATF2, TCF20, MEIS2, DMD, TFDP2, AGRN, TCF4, PLAGL2, ASXL2, KLF12, ATAD2, WHSC1, MED13L, FOXP1, ATF6, NOTCH2, CSRNP3, ETS1, DMTF1, ZFP740, DCP1A, HIVEP1, SCMH1, TCF12, ENY2, BACH2, PAX6, GO:0045449~regulation CTCF, ZEB2, ZEB1, 9430076C15RIK, GLI3, PCGF3, 115 12.89 0.033921905 510 1426 7436 1.18 1 0.558077924 44.94985663 of transcription LRRFIP1, YAP1, NRG1, ATF7IP, ZFP423, ZBTB20, ZFP553, ZCCHC11, SSBP2, SOX11, SNAPC3, ADNP, CDK8, TLE4, RB1, SPEN, HLTF, ZFP26, NCOA2, HIPK1, NCOA5, HIPK2, KHSRP, MDM4, THOC1, CTNND2, CTNND1, NFYB, NEO1, ARID2, NPAS3, TSC22D2, PRDM10, BCL11A, CEBPZ, ETV1, TCEA1, CHD4, MBTPS2, JARID2, NLK, AFF4, AFF3, DACH1, WWTR1, SFPQ, WHSC1L1, GRLF1, PSPC1, ZRANB1, PBX1, RBM14, ZFP60, PBX3, NFIA, NFIB GO:0003002~regionaliz TGFBR1, PAX6, BMPR2, ABI1, ZEB2, GLI3, NCKAP1, 13 1.46 0.034628778 510 98 7436 1.93 1 0.561623016 45.64243399 ation CTNNB1, HIPK1, HIPK2, LRP6, ROR2, PBX1 GO:0043010~camera- PVRL3, NF1, GRLF1, LRP6, PAX6, ZEB1, GLI3, EPHB1, 10 1.12 0.03473217 510 66 7436 2.21 1 0.55872738 45.74304357 type eye development CTNNB1, DSCAM GO:0050803~regulation of synapse structure 4 0.45 0.034792698 510 11 7436 5.30 1 0.555424579 45.80186139 PTK2, APP, AGRN, CTNNA2 and activity GO:0018105~peptidyl- 5 0.56 0.036926864 510 19 7436 3.84 1 0.573458288 47.83774441 TTBK2, NLK, GSK3B, TNKS, AKT3 serine phosphorylation MYO5A, SCD2, GRIK2, NF1, HEXB, CLSTN1, CD24A, GO:0055082~cellular 18 2.02 0.037535031 510 156 7436 1.68 1 0.575623075 48.4045765 KCNK2, ITPR1, QK, APP, GNAQ, ATP2A2, GNB1, FYN, chemical homeostasis PPP3CA, NRG1, CACNA1C GO:0006816~calcium CACNA2D1, ATP2A2, CACHD1, CACNB1, CACNB2, 10 1.12 0.037795756 510 67 7436 2.18 1 0.574341064 48.64579926 ion transport PPP3CA, GRIN3A, CACNA1C, CACNA1D, ITPR1 MYO5A, SCD2, GRIK2, NF1, HEXB, CLSTN1, KCNK2, GO:0050801~ion 19 2.13 0.038126852 510 168 7436 1.65 1 0.573767304 48.95059777 CD24A, ITPR1, QK, EDNRB, APP, GNAQ, ATP2A2, homeostasis GNB1, FYN, PPP3CA, CACNA1C, NRG1 GO:0030900~forebrain DLC1, NF1, PAX6, ZEB2, YWHAE, GLI3, CTNNB1, APP, 14 1.57 0.039242813 510 111 7436 1.84 1 0.580705787 49.96541706 development GNAQ, FYN, NUMB, GRLF1, DCLK1, NFIB GO:0045213~neurotran smitter receptor 3 0.34 0.040709781 510 5 7436 8.75 1 0.590636102 51.27053606 DMD, AGRN, NRG1 metabolic process GO:0000768~syncytiu m formation by plasma 3 0.34 0.040709781 510 5 7436 8.75 1 0.590636102 51.27053606 CDON, NEO1, MYH9 membrane fusion GO:0007520~myoblast 3 0.34 0.040709781 510 5 7436 8.75 1 0.590636102 51.27053606 CDON, NEO1, MYH9 fusion GO:0042493~response CTTNBP2, BLMH, CAPZA2, HIATL1, GNAS, PDE3A, 8 0.90 0.043252521 510 48 7436 2.43 1 0.609602733 53.45707227 to drug SLC35A3, HADHA GO:0042733~embryoni 5 0.56 0.043743601 510 20 7436 3.65 1 0.610151467 53.86856402 IMPAD1, GNAQ, LRP6, GLI3, CTNNB1 c digit morphogenesis GO:0007190~activation of adenylate cyclase 4 0.45 0.0440906 510 12 7436 4.86 1 0.609465156 54.15725592 ADCY3, GNAQ, ADCY5, GNAS activity GO:0030705~cytoskele ton-dependent 6 0.67 0.044646737 510 29 7436 3.02 1 0.610556232 54.61639717 MYO5A, APP, NDEL1, EVL, MYH9, DST intracellular transport GO:0042391~regulation MYO5A, SCD2, GNAQ, GRIK2, FYN, NF1, HEXB, 11 1.23 0.045336368 510 80 7436 2.00 1 0.612734592 55.17973217 of membrane potential PPP3CA, NRG1, KCNK2, QK Yano_Supplemental_Table_S4 Gene ontology – Biological process 7 of 9

Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0001841~neural 7 0.78 0.047425298 510 39 7436 2.62 1 0.626142905 56.84617245 DLC1, ENAH, SHROOM3, GRLF1, ZEB2, NCKAP1, ZIC2 tube formation GO:0070507~regulatio n of 6 0.67 0.050683027 510 30 7436 2.92 1 0.647682569 59.3289795 CTTNBP2, CAPZA2, NPM1, CLASP2, MID1, DST cytoskeleton organization GO:0008217~regulatio 6 0.67 0.050683027 510 30 7436 2.92 1 0.647682569 59.3289795 EDNRB, BMPR2, WNK1, NRG1, CACNA1C, TPM1 n of blood pressure GO:0051656~establish ment of organelle 6 0.67 0.050683027 510 30 7436 2.92 1 0.647682569 59.3289795 MYO5A, FMN2, PTK2, NPM1, NLGN1, MYH9 localization DLC1, ENAH, SHROOM3, CAPZA2, BMPR2, ZEB2, GO:0035295~tube 18 2.02 0.050758772 510 162 7436 1.62 1 0.644761645 59.38507297 GLI3, SHANK3, FOXP1, CTNNB1, ZIC2, NCKAP1, development DDR1, LAMA1, CTTNBP2, GRLF1, PBX1, NFIB GO:0044057~regulatio GRM3, ICA1, PTPRM, ATP2A2, GRIK2, NF1, NLGN1, 13 1.46 0.051092155 510 104 7436 1.82 1 0.643780274 59.63109731 n of system process BMPR2, CTNND2, PPP3CA, PBX3, CACNA1C, TPM1 GO:0007224~smoothe 5 0.56 0.051217182 510 21 7436 3.47 1 0.641282293 59.72300044 HIPK1, CDON, HIPK2, PAX6, GLI3 ned signaling pathway GO:0045761~regulatio n of adenylate cyclase 5 0.56 0.051217182 510 21 7436 3.47 1 0.641282293 59.72300044 ADCY3, GNAQ, ADCY5, NF1, GNAS activity GO:0031279~regulatio 5 0.56 0.051217182 510 21 7436 3.47 1 0.641282293 59.72300044 ADCY3, GNAQ, ADCY5, NF1, GNAS n of cyclase activity GO:0051339~regulatio 5 0.56 0.051217182 510 21 7436 3.47 1 0.641282293 59.72300044 ADCY3, GNAQ, ADCY5, NF1, GNAS n of lyase activity GO:0018210~peptidyl- 4 0.45 0.054487618 510 13 7436 4.49 1 0.661262003 62.0581171 NLK, TNKS, MAPK8, AKT3 threonine modification GO:0009798~axis 4 0.45 0.054487618 510 13 7436 4.49 1 0.661262003 62.0581171 LRP6, PAX6, NCKAP1, CTNNB1 specification GO:0018107~peptidyl- threonine 4 0.45 0.054487618 510 13 7436 4.49 1 0.661262003 62.0581171 NLK, TNKS, MAPK8, AKT3 phosphorylation GO:0048538~thymus 4 0.45 0.054487618 510 13 7436 4.49 1 0.661262003 62.0581171 JARID2, TGFBR1, PBX1, CTNNB1 development GO:0045165~cell fate NOTCH2, ERBB4, CDON, TGFBR1, SOX5, PAX6, SOX6, 10 1.12 0.055871594 510 72 7436 2.03 1 0.667372323 63.00735671 commitment NRG1, GLI3, CTNNB1 LMO3, MORF4L2, CBX3, CNOT2, RORB, RORA, CNOT7, CTNNB1, CNOT4, ESF1, ZFP93, CASP8AP2, ZFP687, ZFP273, MED14, PIAS2, CNBP, TSHZ2, SOX5, MYEF2, SOX6, ATF2, TCF20, TFDP2, TCF4, ASXL2, KLF12, ATAD2, WHSC1, MED13L, FOXP1, NOTCH2, CSRNP3, ETS1, DMTF1, ZFP740, HIVEP1, SCMH1, TCF12, ENY2, BACH2, PAX6, ZEB2, CTCF, ZEB1, GO:0006350~transcrip 9430076C15RIK, GLI3, PCGF3, LRRFIP1, ATF7IP, 97 10.87 0.057397307 510 1208 7436 1.17 1 0.674209309 64.02786283 tion ZFP423, ZBTB20, ZFP553, SSBP2, SOX11, SNAPC3, ADNP, CDK8, TLE4, SPEN, RB1, HLTF, ZFP26, NCOA2, HIPK1, NCOA5, HIPK2, KHSRP, THOC1, CTNND2, CTNND1, NFYB, CDC73, NPAS3, BCL11A, PRDM10, CEBPZ, ETV1, TCEA1, CHD4, MBTPS2, JARID2, NLK, AFF4, AFF3, DACH1, WWTR1, SFPQ, WHSC1L1, PSPC1, GRLF1, PBX1, ZFP60, PBX3, RBM14, NFIA, NFIB GO:0035239~tube DLC1, ENAH, SHROOM3, ZEB2, GLI3, SHANK3, 13 1.46 0.057596644 510 106 7436 1.79 1 0.672236733 64.15921765 morphogenesis NCKAP1, ZIC2, CTNNB1, LAMA1, DDR1, GRLF1, PBX1 GO:0060042~retina morphogenesis in 3 0.34 0.058337495 510 6 7436 7.29 1 0.673801539 64.64345635 PVRL3, LRP6, DSCAM camera-type eye GO:0006949~syncytiu 3 0.34 0.058337495 510 6 7436 7.29 1 0.673801539 64.64345635 CDON, NEO1, MYH9 m formation Yano_Supplemental_Table_S4 Gene ontology – Biological process 8 of 9

List Pop Pop Fold GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0007519~skeletal muscle tissue 7 0.78 0.058340129 510 41 7436 2.49 1 0.670597292 64.64516724 APP, DMD, TNC, NF1, PPP3CA, AGRN, FOXP1 development GO:0019933~cAMP- 5 0.56 0.05934254 510 22 7436 3.31 1 0.673825518 65.2905315 GNAQ, ADCY5, GNAS, RIMS2, CACNA1D mediated signaling GO:0018209~peptidyl- 5 0.56 0.05934254 510 22 7436 3.31 1 0.673825518 65.2905315 TTBK2, NLK, GSK3B, TNKS, AKT3 serine modification GO:0030817~regulation of cAMP biosynthetic 5 0.56 0.05934254 510 22 7436 3.31 1 0.673825518 65.2905315 ADCY3, GNAQ, ADCY5, NF1, GNAS process GO:0045597~positive XRCC6, PAX6, RB1, CDH4, GLI3, CTNNB1, NTRK3, regulation of cell 13 1.46 0.061047848 510 107 7436 1.77 1 0.681332826 66.36299759 SMAP1, ETS1, CDON, GNAS, NRG1, AP3B1 differentiation GO:0008015~blood CTTNBP2, EDNRB, CAPZA2, BMPR2, WNK1, NRG1, 8 0.90 0.062348384 510 52 7436 2.24 1 0.686131942 67.15983391 circulation CACNA1C, TPM1 GO:0003013~circulator CTTNBP2, EDNRB, CAPZA2, BMPR2, WNK1, NRG1, 8 0.90 0.062348384 510 52 7436 2.24 1 0.686131942 67.15983391 y system process CACNA1C, TPM1 GO:0060538~skeletal muscle organ 7 0.78 0.064315448 510 42 7436 2.43 1 0.694694763 68.33133336 APP, DMD, TNC, NF1, PPP3CA, AGRN, FOXP1 development GO:0006887~exocytosi MYO5A, CADPS, SCFD1, CADPS2, STXBP5, NLGN1, 10 1.12 0.06444256 510 74 7436 1.97 1 0.692376141 68.40566542 s EXOC4, SNAP23, RIMS2, CACNA1C GO:0060284~regulation NF1, XRCC6, PAX6, NLGN1, SOX5, CD24A, CDH4, TTC3, 13 1.46 0.06463365 510 108 7436 1.76 1 0.690450882 68.51710044 of cell development NTRK3, PTK2, CDON, PBX1, AGRN GO:0007157~heterophil 4 0.45 0.065937414 510 14 7436 4.17 1 0.694933096 69.26757202 CADM1, CDH2, CDH4, CD24A ic cell adhesion MYO5A, SCD2, GRIK2, NF1, HEXB, CLSTN1, KCNK2, GO:0019725~cellular 22 2.47 0.066893574 510 217 7436 1.48 1 0.697348271 69.80720736 CD24A, ITPR1, QK, APP, NXN, GNAQ, ATP2A2, LARGE, homeostasis FYN, GNB1, DMD, NPM1, PPP3CA, CACNA1C, NRG1 GO:0000122~negative ATF7IP, KLF12, JARID2, TLE4, RB1, ZEB1, SOX6, regulation of 16 1.79 0.067132974 510 144 7436 1.62 1 0.695732825 69.94091474 WWTR1, FOXP1, CTNNB1, NCOA2, HIPK1, HIPK2, transcription from RNA HIVEP1, MDM4, TCF4 polymerase II promoter GO:0031110~regulation of microtubule 5 0.56 0.068110007 510 23 7436 3.17 1 0.698218136 70.48083631 CTTNBP2, CAPZA2, CLASP2, MID1, DST polymerization or depolymerization GO:0001667~ameboidal 5 0.56 0.068110007 510 23 7436 3.17 1 0.698218136 70.48083631 SGPL1, EDNRB, LRP6, ZEB2, NCKAP1 cell migration GO:0007156~homophili CDH13, CADM1, FAT3, PVRL3, CLSTN1, PCDHGA8, 10 1.12 0.069023591 510 75 7436 1.94 1 0.700305472 70.97741706 c cell adhesion PCDH9, CDH2, CDH4, PCDH19 GO:0051960~regulation NTRK3, PTK2, NF1, XRCC6, SOX5, NLGN1, PAX6, PBX1, of nervous system 12 1.35 0.07056192 510 98 7436 1.79 1 0.705674616 71.79583818 AGRN, CDH4, CD24A, TTC3 development GO:0000226~microtubu CTTNBP2, FMN2, PTK2, NDEL1, CAPZA2, CNTROB, le cytoskeleton 11 1.23 0.072443523 510 87 7436 1.84 1 0.712646975 72.76732986 NPM1, TBCE, MYH9, DST, HOOK3 organization MYO5A, SEC24B, AP1G1, LRBA, NBEA, EPS15L1, RIMS2, CD24A, HOOK3, CTNNB1, RTN3, GOLGA7, APP, GO:0016192~vesicle- STX17, EXOC4, RAB6B, SNAP23, SAR1B, AP3B1, 33 3.70 0.072570551 510 359 7436 1.34 1 0.710486873 72.83176673 mediated transport LRP1B, DENND1A, NLGN1, COG3, CADPS, SCFD1, CADPS2, STXBP5, FNBP1L, ARF4, RAB5A, LRP6, ERC1, CACNA1C GO:0044087~regulation ATF7IP, CTTNBP2, PTK2, TGFBR1, CAPZA2, TMSB4X, of cellular component 9 1.01 0.074336612 510 65 7436 2.02 1 0.716647443 73.71287287 EVL, AGRN, CD24A biogenesis GO:0030802~regulation of cyclic nucleotide 5 0.56 0.077505732 510 24 7436 3.04 1 0.729347806 75.2268649 ADCY3, GNAQ, ADCY5, NF1, GNAS biosynthetic process GO:0030814~regulation of cAMP metabolic 5 0.56 0.077505732 510 24 7436 3.04 1 0.729347806 75.2268649 ADCY3, GNAQ, ADCY5, NF1, GNAS process GO:0030808~regulation of nucleotide 5 0.56 0.077505732 510 24 7436 3.04 1 0.729347806 75.2268649 ADCY3, GNAQ, ADCY5, NF1, GNAS biosynthetic process GO:0019935~cyclic- nucleotide-mediated 5 0.56 0.077505732 510 24 7436 3.04 1 0.729347806 75.2268649 GNAQ, ADCY5, GNAS, RIMS2, CACNA1D signaling GO:0010578~regulation of adenylate cyclase 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 GNAQ, ADCY5, GNAS activity involved in G- protein signaling GO:0006998~nuclear 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 NDEL1, TTBK2, ZMPSTE24 envelope organization Yano_Supplemental_Table_S4 Gene ontology – Biological process 9 of 9

Fold List Pop Pop GO Term Count % PValue Bonferroni Benjamini FDR Genes Total Hits Total Enrichment GO:0014902~myotube 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 CDON, NEO1, MYH9 differentiation GO:0010256~endomem 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 NDEL1, TTBK2, ZMPSTE24 brane organization GO:0007189~activation of adenylate cyclase 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 GNAQ, ADCY5, GNAS activity by G-protein signaling pathway GO:0010579~positive regulation of adenylate cyclase activity by G- 3 0.34 0.07804732 510 7 7436 6.25 1 0.729202844 75.47723206 GNAQ, ADCY5, GNAS protein signaling pathway GO:0007422~periphera l nervous system 4 0.45 0.078384813 510 15 7436 3.89 1 0.728102419 75.63204191 EDNRB, NF1, TBCE, NRG1 development GO:0006470~protein PTPRK, PTPRD, PTPRM, PTPRZ1, PTPRG, PPP2CA, amino acid 11 1.23 0.081732816 510 89 7436 1.80 1 0.740802718 77.11871505 SSH2, PPP1R12A, PTPRS, PPM1L, PTPRT dephosphorylation GO:0034621~cellular PRPF31, TDRD3, ENAH, HIST1H2BE, CAPZA2, TBCE, macromolecular 18 2.02 0.082904605 510 173 7436 1.52 1 0.743379836 77.61854037 EIF2A, EVL, IPO9, CTTNBP2, PTK2, H3F3B, AGRN, complex subunit PTBP2, NRG1, DIAP2, SMARCA2, KPNB1 organization GO:0007423~sensory DDR1, RPGR, MEIS2, PVRL3, NF1, GRLF1, PAX6, LRP6, 14 1.57 0.085033836 510 125 7436 1.63 1 0.750012363 78.50053892 organ development RORB, ZEB1, GLI3, EPHB1, CTNNB1, DSCAM GO:0001503~ossificati IMPAD1, NF1, PTN, MAPK8, GNAS, WWTR1, CBFB, 8 0.90 0.08587449 510 56 7436 2.08 1 0.751020388 78.83966375 on WWOX GO:0044093~positive ADCY3, HMGB2, ADCY5, NF1, ZEB2, DGKH, CD24A, regulation of molecular 18 2.02 0.086365753 510 174 7436 1.51 1 0.75055054 79.03550209 NDEL1, GNAQ, HIPK1, CASP8AP2, GNB1, SERINC1, function NPM1, HIPK2, GNAS, BRD4, NRG1 GO:0008344~adult 6 0.67 0.087646069 510 35 7436 2.50 1 0.753363106 79.53789671 EPHA4, APP, HIPK2, TBCE, PBX3, CACNA1C locomotory behavior GO:0050905~neuromus 6 0.67 0.087646069 510 35 7436 2.50 1 0.753363106 79.53789671 MYO5A, APP, ADCY5, HEXB, GRIN3A, CTNNA2 cular process CBX3, ZEB2, CTCF, ZEB1, SOX6, GLI3, CTNNB1, GO:0010629~negative MOV10, NRG1, TCF4, ATF7IP, ZCCHC11, KLF12, regulation of gene 26 2.91 0.090797325 510 276 7436 1.37 1 0.763590422 80.72655956 JARID2, TLE4, SPEN, RB1, WWTR1, FOXP1, NCOA2, expression HIPK1, HIPK2, ZRANB1, HIVEP1, MDM4, SCMH1 ADCY3, ADCY5, RHOQ, FGF13, ARHGAP5, TLK1, RAB6B, PLCB1, NRG1, ARL5B, RAPGEF1, PAG1, NET1, ROCK1, PI4KA, PRKCE, MARK1, DEPDC5, MAP4K3, GO:0007242~intracellul MAP4K4, NCOA2, HIPK1, GNAQ, GNB1, UBR5, HIPK2, 52 5.83 0.090932211 510 619 7436 1.22 1 0.761675002 80.77595761 ar signaling cascade RAB5A, ROR2, MAPK8, GNAS, PPM1L, RAB12, RALGPS2, RIMS2, AZI2, PLCL1, AGRP, DCLK1, DVL3, RAB8B, NLK, MAP2K4, NF1, DGKH, SHANK3, ICK, GSK3B, ARF4, BRE, GRLF1, RAB39, CACNA1D GO:0050767~regulation NTRK3, PTK2, NF1, XRCC6, SOX5, NLGN1, PAX6, 11 1.23 0.091721003 510 91 7436 1.76 1 0.762340087 81.06244823 of neurogenesis PBX1, CDH4, CD24A, TTC3 GO:0043627~response 4 0.45 0.091767899 510 16 7436 3.65 1 0.760106745 81.07935379 CTTNBP2, TGFBR1, CAPZA2, CD24A to estrogen stimulus HMGB2, BCAT2, CADM1, TDRD7, DZIP1, TGFBR1, GO:0048609~reproduct ADCYAP1R1, CAPZA2, HEXB, AFF4, PDE3A, HERC2, ive process in a 21 2.35 0.095143737 510 214 7436 1.43 1 0.770630389 82.25963422 HNRPLL, QK, CTTNBP2, FMN2, NPAS3, RAD18, multicellular organism STRBP, PPP2R2B, DIAP2 HMGB2, BCAT2, CADM1, TDRD7, DZIP1, TGFBR1, GO:0032504~multicellu ADCYAP1R1, CAPZA2, HEXB, AFF4, PDE3A, HERC2, lar organism 21 2.35 0.095143737 510 214 7436 1.43 1 0.770630389 82.25963422 HNRPLL, QK, CTTNBP2, FMN2, NPAS3, RAD18, reproduction STRBP, PPP2R2B, DIAP2 GO:0030902~hindbrain 6 0.67 0.096363149 510 36 7436 2.43 1 0.772798456 82.66864868 DLC1, PLXNA2, MYO16, RORA, CTNNA2, NFIB development GO:0045637~regulation of myeloid cell 6 0.67 0.096363149 510 36 7436 2.43 1 0.772798456 82.66864868 SMAP1, ETS1, NF1, GNAS, RB1, CTNNB1 differentiation GO:0014706~striated APP, DMD, TNC, NF1, PPP3CA, AGRN, NRG1, TPM1, muscle tissue 9 1.01 0.097580524 510 69 7436 1.90 1 0.774915121 83.06810527 FOXP1 development GO:0030799~regulation of cyclic nucleotide 5 0.56 0.098108132 510 26 7436 2.80 1 0.77451451 83.23852076 ADCY3, GNAQ, ADCY5, NF1, GNAS metabolic process GO:0007218~neuropep 5 0.56 0.098108132 510 26 7436 2.80 1 0.77451451 83.23852076 LPHN2, LPHN3, BAI1, BAI3, AGRP tide signaling pathway GO:0030534~adult 7 0.78 0.099345319 510 47 7436 2.17 1 0.776653964 83.63181088 EPHA4, APP, HIPK2, TBCE, PBX3, CACNA1C, AGRP behavior GO:0016339~calcium- dependent cell-cell 3 0.34 0.099472812 510 8 7436 5.47 1 0.774834328 83.67184184 NLGN1, PCDHGA8, CDH2 adhesion