[发明专利]预测新抗原负荷和检测基因组突变的基因panel

摘要

本发明涉及生物技术、DNA突变检测技术和生物信息学领域，尤其涉及一种预测新抗原负荷和检测基因组突变的基因panel。具体而言，本发明涉及一个组合了839个基因的基因panel，结合511个基因融合事件，本发明基因panel能够快速、高效、准确地对新抗原负荷进行预测，还可一次性检测多个位点的DNA突变，以便在癌症免疫治疗过程中根据患者的基因组特征选择最优的个体化治疗药物及方案，此外，本发明基因panel还可用于测量SNV、Indel、CNV、基因融合、MSI、TMB、HLA等多种类型的生物标志物。

主权项

1.一种预测新抗原负荷和检测基因组突变的基因panel，其特征在于：所述基因panel上包含28,888个用于捕获靶向DNA的靶向DNA探针和511个用于捕获基因与基因DNA融合的融合DNA探针；/n其中所述靶向DNA是指人类基因组上下述839个基因的外显子区域：ANO10,AAAS,ABCA1,ABCC3,ABL1,ABL2,ABLIM1,ACIN1,ACOT7,ACSL1,ACTG1,ACTR1B,ACVR1B,ACVR2A,ADAM15,ADAMTS12,ADAR,LPHN2,ADIPOR1,ADNP,ADNP2,AGK,AHCTF1,AHNAK,AHNAK2,AIMP2,AKAP9,AKT1,AKT2,AKT3,ALDH4A1,ALG5,ALK,ALKBH2,ALPK2,AMER1,ANAPC5,ANKLE2,ANKRD12,ANO6,AP4B1,APC,AR,ARAF,AREL1,ARFGEF1,ARFGEF2,ARHGAP17,ARHGAP35,ARHGEF7,ARID1A,ARID2,ARMC5,ASAH2,ASPM,ASXL1,ATM,ATP11B,ATP11C,ATP2A2,ATP6V0D1,ATR,ATRN,ATRX,AXIN1,AXIN2,AXL,B2M,BAP1,BARD1,BAZ1B,BCL2,BCL2L11,BCL6,BCLAF1,BCOR,BCORL1,BICD2,GLTSCR1L,BIRC3,BLM,BLVRA,BMS1,BOD1L1,BRAF,BRAT1,BRCA1,BRCA2,BRIP1,BRWD1,BTAF1,BTK,BTN3A2,C10orf88,C11orf80,C6orf203,CACTIN,CAD,CALR,CAMSAP1,CAMTA2,CAND1,CARD11,CASP5,CASP8,CBL,CCDC168,CCDC43,CCND1,CCND2,CCND3,CCNE1,CD163,CD1C,CD274,CD93,CDC16,CDC25B,CDH1,CDK12,CDK4,CDK6,CDKN2A,CDS1,CEBPA,CEP104,CEP290,CHAF1A,CHD4,CHEK1,CHEK2,CIC,CIRBP,CLCN6,CLK2,CLSTN1,CMKLR1,CNKSR1,CNOT1,RQCD1,COL12A1,COL14A1,COL6A3,COPS2,COX10,CPSF6,CPXM2,CREBBP,CRMP1,CRNKL1,CSDE1,CSF3R,CSNK2A2,CSPG4,CTCF,CTNNB1,CTNND1,CUL1,CUL3,CUX1,CXCR4,CYLD,CYP4B1,DAB2,DCHS1,DCLRE1A,DDR2,DDX27,DDX54,DDX58,DECR1,DENND1A,DHPS,DHX15,DHX29,DHX30,DHX35,DHX38,DHX9,DIAPH3,DIS3,DMBT1,DNAJA2,DNAJC10,DNMT3A,DOCK8,DPP3,DSP,DYRK1A,DYRK1B,DYSF,ECSIT,EDEM1,EDEM2,EDNRB,EFTUD2,EGFR,EIF2AK3,EIF4ENIF1,ELF1,ELF3,ELMO2,ELOVL1,EMC2,EML3,EML4,ENC1,ENPP2,ENTPD4,ENTPD6,EPB41L3,EPCAM,EPHB2,ERBB2,ERBB3,ERBB4,ERCC5,ERMP1,ESR1,ESRP1,ESYT1,ETAA1,ETV6,EXOC2,EZH2,FAHD2A,FAM160A2,FAM208A,FAM83B,FAM8A1,FANCA,FANCC,FANCD2,FANCE,FANCF,FANCG,FANCI,FANCL,FANCM,FARS2,FASTKD3,FASTKD5,FAT1,FBXO4,FBXO42,FBXW7,FERMT3,FES,FGF19,FGF3,FGF4,FGFR1,FGFR2,FGFR3,FGFR4,FLAD1,FLNB,FLT1,FLT3,FMR1,FNDC3A,FNIP1,FOXL2,FOXO1,FOXP1,FPGT,FRY,FSCB,FUBP1,FYN,GABPB1,GANAB,GATA2,GBE1,GBF1,GCDH,GIMAP7,GLI1,GNA11,GNAQ,GNAS,GOLGA3,GOLGB1,GPR137,GPRC5C,GRB14,GRINA,GSDMD,GSK3B,GTF2F1,GTPBP2,GXYLT1,H3F3A,H6PD,HCK,HCST,HEATR1,HEPH,HEXA,HEXDC,HLA-A,HLA-B,HLA-C,HLA-DQB1,HLA-DRB1,HMG20A,HNRNPH1,HNRNPM,HOXB13,HPS1,HRAS,HSD11B1,HSP90AB1,IARS2,IDH1,IDH2,IDS,IFNGR1,IFNGR2,IGF1R,IGF2R,IGSF8,IKBKE,IKZF1,IL7R,IMP4,INHBA,INTS3,INTS5,INTS8,IRF1,IRF3,IRS4,ITGB2,ITPR3,JAK1,JAK2,JAK3,CSRP2BP,KAT6A,KCNMA1,KDM3A,KDR,KEAP1,KIAA0232,KIAA0355,ZSWIM8,KIAA0930,KIAA1279,KIFAP3,KIN,KIT,KLHL36,KMT2C,KRAS,LAIR1,LAMA3,LANCL2,LARP4B,LENG8,LIG4,LILRB4,HNRNPCP5,LONP1,LPIN2,LRBA,LRRC41,LRRIQ3,LTN1,MADD,MAGT1,MAN2B1,MAP2K1,MAP2K2,MAP2K3,MAP2K7,MAPK1,MARK2,MBD1,MBNL1,MCCC1,MCHR2,MCM7,MDM2,MDM4,MECOM,MED13L,MED16,MED25,MEN1,MET,METTL17,MFSD1,MGA,MGAT4B,MINK1,MLH1,MPL,MRE11A,MRPL15,MRPL39,MRPS2,MKL1,MSH2,MSH3,MSH6,MTHFR,MTM1,MTOR,MUT,MUTYH,MXRA5,MYC,MYCN,MYD88,MYO3A,MYO9A,MYOF,NAT10,NBN,NCF4,NCOA6,NDUFAF1,NDUFC2,NF1,NF2,NFE2L2,NFIC,NFIX,NID1,NIPBL,NOC4L,NOL8,NOM1,NOTCH1,NOTCH2,NOTCH3,NOTCH4,NPM1,NR1H2,NR4A2,NRAS,NTHL1,NTRK1,NTRK2,NTRK3,NUDCD1,NUP155,OAS1,OFD1,OR6C68,OXSM,PABPC1,PAK1,PALB2,PAN2,PANK4,PARP14,PARP4,PBRM1,PCCB,PCDH17,PCMTD1,PDCD1LG2,PDGFRA,PDGFRB,PELP1,PEX1,PGAP1,PGAP2,PGM2,PGS1,PHF1,PHF3,PHF6,PHRF1,PIAS4,PIGB,PIGO,PIGQ,PIK3C2G,PIK3CA,PIK3CB,PIK3R1,PKM,PLCB3,PLCG2,PLEC,PLXNA1,PLXND1,PMS1,PMS2,PNPLA8,POLD1,POLE,POLE2,POLR2B,POLR3A,POLR3B,POM121,POT1,PPIL2,PPM1B,SMEK1,PPT1,PRAMEF4,PRDM10,PRDM2,PREX1,PRKACA,PRKAR1A,PRKD2,PRPF31,PRPF6,PSMC4,PSMD2,PSMD9,PSME4,PTCH1,PTEN,PTK2B,PTPN11,PTPN6,PTPRA,PTPRC,PXDN,PXK,QRICH1,QSOX1,QSOX2,R3HDM1,RAB3GAP1,RAC1,RAD50,RAD51,RAD51B,RAD51C,RAD51D,RAD54L,RAD54L2,RAF1,RARA,RB1,RB1CC1,RBM10,RBM12,RBM15,RBMX,RECQL,REL,RET,REV3L,RFC1,RHOA,RHOT2,KIAA1432,RIC8A,RIF1,RNF111,RNF128,RNF145,RNF43,ROBO4,ROS1,RPA1,RPRD2,RPS6KC1,RRP12,RUNX1,SAMD9L,SBNO1,SCAP,SCFD2,SCYL2,SDR16C5,SDSL,SEC23B,SEC23IP,SEC24B,SEC31A,SELP,SEMA4C,SENP1,SEPT6,SERPINB10,SERPINB3,SETBP1,SETD1B,SETD2,SETDB1,SETX,SF1,SF3A3,SF3B1,SH2B1,SIDT2,SIRPA,SLAMF1,SLC12A7,SLC16A4,SLC23A2,SLC25A5,SLC25A6,SLC35F5,SLC39A3,SLC3A2,SLC41A3,SLC5A6,SLC9A6,SLIT2,SMAD3,SMAD4,SMARCA4,SMARCB1,SMC5,SMC6,SMG5,SMO,SNRNP200,SNRPB,SNRPN,SNX19,SNX27,SOCS1,SPAG9,SPOPL,SPRED2,SPTBN1,SPTLC2,SRBD1,SRP72,SRPR,SRSF2,ST3GAL3,STAG2,STAT1,STAT3,STAT5B,STAU2,STEAP3,STK11,STX3,SUCLG2,SUCO,SUN1,SUPT5H,SYCP2,SYNE1,TAB1,TAF1C,TAF1D,TAF3,TAOK3,TAP1,TAP2,TATDN1,TBC1D17,TCEB3,TCF12,TCF20,TCF7L2,TDG,TDRD1,TEAD2,TERT,TET2,TEX10,TFE3,TGFBR2,TGFBRAP1,THAP7,TICAM1,TIMELESS,TIMM44,TIPARP,TJP2,TLE3,TMEM168,SLC35G2,TMEM39B,TMEM57,TMEM63B,TMEM79,TNIP1,TNPO1,TNPO3,TNRC6A,TOP3A,TP53,TP53BP1,TPST2,TRAF7,TRAK1,TRAPPC9,TRIB3,TRIM21,TRIM33,TRIM35,TRMT1,TRMT2A,TRPS1,TRRAP,TSC1,TSC2,TTC7A,TTI1,TTK,TTLL1,TUBGCP2,TUSC3,ZCCHC6,U2AF1,UBA6,UBE4A,UBR2,UFL1,UGGT1,ULK1,UPF2,URGCP,USF1,USP26,USP32,USP38,USP5,USP9X,DIEXF,VCAN,VHL,VIPAS39,VPS13A,VPS13C,VPS33A,C16ORF62,VRK3,WAC,KIAA1033,WDR25,WDR45,WDR6,WDR60,WDR81,WT1,WWC3,XRN2,XYLT2,YAP1,YARS2,YIF1A,YIPF2,YME1L1,ZBTB38,ZC3H18,ZC3HAV1,ZFHX3,ZFP36L2,ZFP37,ZFP82,ZFR,ZHX2,ZMYM3,ZNF148,ZNF223,ZNF318,ZNF609,ZNF777,ZRSR2,BMPR1A,GREM1,KLLN,GALNT12,ABRAXAS1,GEN1,MC1R,MITF,PTCH2,SUFU,PRKACB,RECQL4,CDKN1B,SDHA,SDHB,SDHC,SDHD,SDHAF2,EPAS1,MAX,MDH2,TMEM127,DICER1,FLCN,CDC73,FH,CTR9,REST,TRIM37,GPC3,GPC4,BUB1B,DIS3L2,PAX6,WRN,RHBDF2,VSIG10L,CFTR,SPINK1,PRSS1,EXT1,EXT2,FANCB,XRCC2,MAD2L2,SLX4,UBE2T,SMARCE1,MTAP,PHOX2B,FOXE1,KIF1B,SLC25A11,DLST,ANKRD26,DDX41,PAX5,DDB2,ERCC1,ERCC2,ERCC3,ERCC4,POLH,XPA,XPC,SOS1,RIT1,SBDS,EFL1,DNAJC21,SRP54,SAMD9；/n所述基因与基因DNA融合是指下述人类基因对融合产生的DNA片段：ATIC-ALK,BCL2L11-BCL2L11,BCR-ABL1,C2orf44-ALK,CARS-ALK,CCDC6-RET,CD74-NRG1,CD74-ROS1,CLIP1-ROS1,CLTC-ALK,DCTN1-ALK,EML4-ALK,ERC1-RET,ERC1-ROS1,ETV6-NTRK3,EZR-ROS1,FGFR1-TACC1,FGFR1-ZNF703,FGFR3-BAIAP2L1,FGFR3-TACC3,FN1-ALK,GOLGA5-RET,GOPC-ROS1,HIP1-ALK,HLA-A-ROS1,HOOK3-RET,KIAA1598-ROS1,KIF5B-ALK,KIF5B-RET,KLC1-ALK,LMNA-NTRK1,LRIG3-ROS1,MSN-ALK,MYO5A-ROS1,NACC2-NTRK2,NPM1-ALK,NTRK3-ETV6,PCM1-RET,PPFIBP1-ALK,PPFIBP1-ROS1,PRKAR1A-RET,PWWP2A-ROS1,QKI-NTRK2,RANBP2-ALK,SDC4-ROS1,SEC31A-ALK,SLC34A2-ROS1,SQSTM1-ALK,STRN-ALK,TP53-NTRK1,TPM3-ALK,TPM3-NTRK1,TPM3-ROS1,TPM4-ALK,TRIM24-RET,TRIM27-RET,TRIM33-RET,VCL-ALK。/n