Supplementary Table S6. Gene Ontology Enrichment Analysis of Module1 and Module2 in PPI Network

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Supplementary Table S6. Gene ontology enrichment analysis of module1 and module2 in PPI network.

Group Category Term Count PValue Genes GO:0007067~mitotic nuclear CDK1, NUF2, TPX2, CENPF, ANLN, CDC20, NDC80, AURKA, Module1 BP division 14 4.53E-15 BIRC5, PBK, PTTG1, FAM83D, CCNA2, ASPM CDK1, NUF2, TPX2, CENPF, BIRC5, AURKA, CDC20, NDC80, Module1 BP GO:0051301~cell division 15 1.39E-14 PTTG1, FAM83D, CCNB1, MAD2L1, NCAPG, CKS2, CCNA2 PRC1, TPX2, NUSAP1, CENPF, TTK, AURKA, BIRC5, CDC20, Module1 CC GO:0005819~spindle 9 1.24E-10 KIF20A PRC1, AURKA, PTTG1, TYMS, NCAPG, TOP2A, CCNA2, ASPM, TRIP13, GINS1, CDK1, DTL, DLGAP5, TPX2, NUF2, Module1 NUSAP1, CENPF, NDC80, BIRC5, CDC20, MCM2, PBK, CENPK, CDKN3, MCM3, CCNB1, UHRF1, MAD2L1, RRM2, CC GO:0005634~nucleus 31 4.82E-10 MELK, UBE2T Module1 CC GO:0030496~midbody 8 7.95E-09 CDK1, KIF4A, PRC1, CENPF, AURKA, BIRC5, ASPM, KIF20A GINS1, CDK1, KIF4A, PRC1, DTL, TPX2, CENPF, BIRC5, Module1 AURKA, ANLN, CDC20, MCM2, CENPK, MCM3, CCNB1, CC GO:0005654~nucleoplasm 22 1.39E-08 TYMS, RFC4, RRM2, TOP2A, CCNA2, UBE2T, KIF20A GO:0005876~spindle Module1 CC microtubule 6 3.07E-08 CDK1, KIF4A, PRC1, NUSAP1, AURKA, BIRC5 GO:0007062~sister chromatid Module1 BP cohesion 7 1.08E-07 MAD2L1, NUF2, CENPF, BIRC5, NDC80, CDC20, CENPK GO:0000086~G2/M transition of Module1 BP mitotic cell cycle 7 5.89E-07 CCNB1, CDK1, TPX2, AURKA, BIRC5, MELK, HMMR

Shi L, et al. J Clin Pathol 2021; 74:504–512. doi: 10.1136/jclinpath-2020-206979 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Clin Pathol

GO:0031145~anaphase- Module1 promoting complex-dependent BP catabolic process 6 9.01E-07 CCNB1, CDK1, MAD2L1, AURKA, CDC20, PTTG1 GO:0042787~protein ubiquitination involved in Module1 ubiquitin-dependent protein BP catabolic process 7 1.13E-06 CCNB1, CDK1, UHRF1, MAD2L1, AURKA, CDC20, PTTG1 FAM83D, CDK1, TYMS, UHRF1, DLGAP5, CKS2, TPX2, Module1 BP GO:0008283~cell proliferation 9 1.30E-06 CENPF, MELK Module1 CC GO:0000922~spindle pole 6 2.99E-06 CCNB1, MAD2L1, PRC1, TPX2, CENPF, CDC20 GO:0000082~G1/S transition of Module1 BP mitotic cell cycle 6 3.21E-06 CDK1, TYMS, RRM2, MCM2, MCM3, CDKN3 KIF4A, PRC1, TTK, AURKA, PTTG1, HMMR, FAM83D, NCAPG, TOP2A, CCNA2, TRIP13, CDK1, DTL, DLGAP5, Module1 TPX2, NUF2, NUSAP1, CENPF, NDC80, BIRC5, CDC20, MCM2, PBK, CENPK, CDKN3, MCM3, CCNB1, UHRF1, RFC4, MF GO:0005515~protein binding 34 6.43E-06 MAD2L1, RRM2, CKS2, MELK, KIF20A CDK1, KIF4A, TPX2, TTK, AURKA, PBK, MCM2, MCM3, Module1 MF GO:0005524~ATP binding 14 1.28E-05 RFC4, TOP2A, UBE2T, MELK, TRIP13, KIF20A GO:0019901~protein kinase CCNB1, FAM83D, PRC1, CKS2, TPX2, AURKA, CCNA2, Module1 MF binding 8 1.79E-05 KIF20A CCNB1, CDK1, DTL, NCAPG, CENPF, AURKA, CDC20, Module1 CC GO:0005813~centrosome 8 2.45E-05 MCM3 Module1 BP GO:0006260~DNA replication 6 2.47E-05 CDK1, RFC4, DTL, RRM2, MCM2, MCM3 GO:0000777~condensed Module1 CC chromosome kinetochore 5 3.16E-05 MAD2L1, NUF2, BIRC5, NDC80, CENPK

Module1 BP GO:0000281~mitotic cytokinesis 4 3.75E-05 KIF4A, NUSAP1, ANLN, KIF20A GO:0007052~mitotic spindle Module1 BP organization 4 4.16E-05 CCNB1, TTK, AURKA, NDC80 GO:0008017~microtubule Module1 MF binding 6 9.76E-05 FAM83D, KIF4A, PRC1, NUSAP1, BIRC5, KIF20A CDK1, KIF4A, PRC1, NUF2, TPX2, CENPF, BIRC5, AURKA, Module1 NDC80, CDC20, PTTG1, CENPK, HMMR, CCNB1, TYMS, CC GO:0005829~cytosol 18 1.46E-04 MAD2L1, NCAPG, RRM2 GINS1, CDK1, KIF4A, PRC1, DTL, DLGAP5, NUSAP1, TTK, CENPF, BIRC5, CDC20, PTTG1, MCM2, CDKN3, FAM83D, Module1 CCNB1, TYMS, NCAPG, RRM2, TOP2A, CCNA2, UBE2T, CC GO:0005737~cytoplasm 23 1.54E-04 ASPM GO:0000775~chromosome, Module1 CC centromeric region 4 2.26E-04 NUF2, CENPF, BIRC5, NDC80 GO:0051310~metaphase plate Module1 BP congression 3 3.24E-04 FAM83D, CENPF, NDC80 Module1 CC GO:0005874~microtubule 6 4.43E-04 KIF4A, TPX2, NUSAP1, AURKA, BIRC5, KIF20A GO:0007059~chromosome Module1 BP segregation 4 4.84E-04 NUF2, CENPF, NDC80, TOP2A GO:0051436~negative regulation of ubiquitin-protein ligase Module1 activity involved in mitotic cell BP cycle 4 5.50E-04 CCNB1, CDK1, MAD2L1, CDC20 GO:0007051~spindle Module1 BP organization 3 5.87E-04 TTK, AURKA, ASPM Module1 CC GO:0000776~kinetochore 4 6.38E-04 MAD2L1, CENPF, TTK, NDC80

GO:0051437~positive regulation of ubiquitin-protein ligase Module1 activity involved in regulation of BP mitotic cell cycle transition 4 6.71E-04 CCNB1, CDK1, MAD2L1, CDC20 GO:0007094~mitotic spindle Module1 BP assembly checkpoint 3 9.23E-04 MAD2L1, CENPF, TTK GO:0000083~regulation of Module1 transcription involved in G1/S BP transition of mitotic cell cycle 3 0.001224 CDK1, TYMS, RRM2 GO:0051439~regulation of Module1 ubiquitin-protein ligase activity BP involved in mitotic cell cycle 3 0.001224 CCNB1, CDK1, CDC20 Module1 BP GO:0007049~cell cycle 5 0.001419 UHRF1, AURKA, CDC20, MCM2, CDKN3 GO:0000070~mitotic sister Module1 BP chromatid segregation 3 0.001448 MAD2L1, NUSAP1, NDC80 GO:0045931~positive regulation Module1 BP of mitotic cell cycle 3 0.001816 CCNB1, CDK1, BIRC5 GO:0015630~microtubule Module1 CC cytoskeleton 4 0.002893 PRC1, TPX2, AURKA, MCM2 Module1 CC GO:0072686~mitotic spindle 3 0.003298 CDK1, MAD2L1, AURKA Module1 BP GO:0000910~cytokinesis 3 0.005268 PRC1, BIRC5, KIF20A Module1 MF GO:0019899~enzyme binding 5 0.006471 RFC4, BIRC5, CDC20, MCM2, TOP2A Module1 CC GO:0031262~Ndc80 complex 2 0.008315 NUF2, NDC80 GO:0000942~condensed nuclear Module1 CC chromosome outer kinetochore 2 0.008315 CCNB1, NDC80

GO:0006977~DNA damage response, signal transduction by Module1 p53 class mediator resulting in BP cell cycle arrest 3 0.008657 CCNB1, CDK1, AURKA GO:0048471~perinuclear region Module1 CC of cytoplasm 6 0.008955 MAD2L1, CENPF, AURKA, CDC20, MCM3, CDKN3 GO:0035173~histone kinase Module1 MF activity 2 0.008975 CCNB1, CDK1 GO:0004674~protein Module1 MF serine/threonine kinase activity 5 0.00984 CDK1, TTK, AURKA, PBK, MELK GO:0032133~chromosome Module1 CC passenger complex 2 0.010384 AURKA, BIRC5 Module1 MF GO:0003682~chromatin binding 5 0.011241 CDK1, CKS2, CENPF, TOP2A, UBE2T Module1 CC GO:0045120~pronucleus 2 0.014508 CENPF, AURKA Module1 CC GO:0043203~axon hillock 2 0.014508 TPX2, AURKA GO:0090267~positive regulation Module1 of mitotic cell cycle spindle BP assembly checkpoint 2 0.015737 MAD2L1, NDC80 Module1 BP GO:0006281~DNA repair 4 0.015922 CDK1, UHRF1, PTTG1, UBE2T Module1 CC GO:0016363~nuclear matrix 3 0.017405 KIF4A, UHRF1, CENPF Module1 CC GO:0072687~meiotic spindle 2 0.018615 AURKA, ASPM Module1 CC GO:0042555~MCM complex 2 0.018615 MCM2, MCM3 Module1 CC GO:0005694~chromosome 3 0.020199 KIF4A, DTL, NUSAP1 GO:0097431~mitotic spindle Module1 CC pole 2 0.020662 FAM83D, ASPM

GO:0031616~spindle pole Module1 CC centrosome 2 0.020662 DLGAP5, AURKA GO:0006268~DNA unwinding Module1 BP involved in DNA replication 2 0.022407 MCM2, TOP2A GO:0055015~ventricular cardiac Module1 BP muscle cell development 2 0.022407 CCNB1, CDK1 GO:0034501~protein localization Module1 BP to kinetochore 2 0.022407 CDK1, TTK GO:0042803~protein Module1 MF homodimerization activity 6 0.022984 TYMS, MAD2L1, CENPF, TTK, BIRC5, TOP2A Module1 CC GO:0005814~centriole 3 0.023168 AURKA, BIRC5, TOP2A GO:0042802~identical protein Module1 MF binding 6 0.025349 UHRF1, MAD2L1, PRC1, BIRC5, NDC80, TRIP13 GO:0000784~nuclear Module1 CC chromosome, telomeric region 3 0.03003 CDK1, MCM2, MCM3 Module1 MF GO:0042393~histone binding 3 0.030745 UHRF1, CKS2, MCM2 Module1 BP GO:0042493~response to drug 4 0.031089 CCNB1, CDK1, TYMS, CENPF GO:0051726~regulation of cell Module1 BP cycle 3 0.031985 CCNB1, DTL, CENPF GO:1901796~regulation of Module1 signal transduction by p53 class BP mediator 3 0.031985 RFC4, TPX2, AURKA GO:0006271~DNA strand Module1 elongation involved in DNA BP replication 2 0.033426 GINS1, RFC4

GO:0007095~mitotic G2 DNA Module1 BP damage checkpoint 2 0.033426 CDK1, CCNA2 GO:0007076~mitotic Module1 BP chromosome condensation 2 0.033426 NCAPG, NUSAP1 CCNB1, CDK1, KIF4A, NCAPG, NUF2, TTK, NDC80, MCM3, Module1 CC GO:0016020~membrane 10 0.0338 MELK, HMMR Module1 MF GO:0048037~cofactor binding 2 0.035431 TYMS, BIRC5 GO:0004842~ubiquitin-protein Module1 MF transferase activity 4 0.037455 UHRF1, DTL, BIRC5, UBE2T Module1 BP GO:0006915~apoptotic process 5 0.038366 CDK1, TPX2, BIRC5, MCM2, MELK Module1 BP GO:0001556~oocyte maturation 2 0.039979 CCNB1, TRIP13 GO:0004672~protein kinase Module1 MF activity 4 0.046529 CDK1, AURKA, PBK, MELK GO:0060045~positive regulation Module1 of cardiac muscle cell BP proliferation 2 0.04865 CCNB1, CDK1 GO:0003678~DNA helicase Module1 MF activity 2 0.052684 MCM2, MCM3 GO:0001578~microtubule Module1 BP bundle formation 2 0.055103 PRC1, KIF20A GO:0048589~developmental Module1 BP growth 2 0.055103 TYMS, ASPM Module1 BP GO:0007283~spermatogenesis 4 0.055909 CCNB1, PTTG1, ASPM, TRIP13 GO:0071897~DNA biosynthetic Module1 BP process 2 0.057244 TYMS, CENPF

GO:0045840~positive regulation Module1 BP of mitotic nuclear division 2 0.057244 NUSAP1, AURKA GO:0046777~protein Module1 BP autophosphorylation 3 0.057668 TTK, AURKA, MELK Module1 BP GO:0048477~oogenesis 2 0.061513 ASPM, TRIP13 GO:0006513~protein Module1 BP monoubiquitination 2 0.061513 DTL, UBE2T GO:0008022~protein C-terminus Module1 MF binding 3 0.063108 CENPF, CDC20, TOP2A GO:0004712~protein Module1 serine/threonine/tyrosine kinase MF activity 2 0.063315 TTK, AURKA Module1 BP GO:0097421~liver regeneration 2 0.06364 TYMS, AURKA GO:0006270~DNA replication Module1 BP initiation 2 0.069994 MCM2, MCM3 GO:0007093~mitotic cell cycle Module1 BP checkpoint 2 0.069994 MAD2L1, TTK GO:0004869~cysteine-type Module1 MF endopeptidase inhibitor activity 2 0.07383 BIRC5, PTTG1 GO:0004693~cyclin-dependent Module1 protein serine/threonine kinase MF activity 2 0.07383 CCNB1, CDK1 Module1 MF GO:0019894~kinesin binding 2 0.075919 FAM83D, PRC1 GO:0043161~proteasome- Module1 mediated ubiquitin-dependent BP protein catabolic process 3 0.077002 CDK1, MAD2L1, CDC20

GO:0042769~DNA damage Module1 response, detection of DNA BP damage 2 0.078401 RFC4, DTL GO:0019985~translesion Module1 BP synthesis 2 0.078401 RFC4, DTL GO:0090307~mitotic spindle Module1 BP assembly 2 0.078401 TPX2, BIRC5 GO:0006974~cellular response Module1 BP to DNA damage stimulus 3 0.080292 DTL, TOP2A, UBE2T GO:0018107~peptidyl-threonine Module1 BP phosphorylation 2 0.082576 CDK1, TTK GO:0043066~negative regulation Module1 BP of apoptotic process 4 0.083072 CDK1, MAD2L1, AURKA, BIRC5 GO:0000079~regulation of Module1 cyclin-dependent protein BP serine/threonine kinase activity 2 0.084657 CDKN3, CCNA2 GO:0007346~regulation of Module1 BP mitotic cell cycle 2 0.086733 CKS2, BIRC5 GO:0008284~positive regulation Module1 BP of cell proliferation 4 0.087783 PRC1, TTK, BIRC5, CDC20 GO:0007077~mitotic nuclear Module1 BP envelope disassembly 2 0.094993 CCNB1, CDK1 GO:0032508~DNA duplex Module1 BP unwinding 2 0.094993 GINS1, MCM3 GO:0005576~extracellular Module2 CC region 7 1.13E-05 MBL2, C9, KLKB1, C6, F9, HGFAC, SPP2

GO:0004252~serine-type Module2 MF endopeptidase activity 4 1.14E-04 MBL2, KLKB1, F9, HGFAC GO:0006958~complement Module2 BP activation, classical pathway 3 9.41E-04 MBL2, C9, C6 Module2 BP GO:0006508~proteolysis 4 0.001314 MBL2, KLKB1, F9, HGFAC GO:0005579~membrane attack Module2 CC complex 2 0.003069 C9, C6 GO:0070062~extracellular Module2 CC exosome 6 0.003234 C9, KLKB1, C6, FTCD, F9, SPP2 GO:0031638~zymogen Module2 BP activation 2 0.004281 KLKB1, F9 GO:0007597~blood coagulation, Module2 BP intrinsic pathway 2 0.008545 KLKB1, F9 GO:0030449~regulation of Module2 BP complement activation 2 0.014206 C9, C6 Module2 CC GO:0005615~extracellular space 4 0.017017 MBL2, KLKB1, F9, HGFAC GO:0006956~complement Module2 BP activation 2 0.040713 MBL2, C6 GO:0006979~response to Module2 BP oxidative stress 2 0.05123 MBL2, TAT

Shi L, et al. J Clin Pathol 2021; 74:504–512. doi: 10.1136/jclinpath-2020-206979