JPWO2021183917A5 - - Google Patents
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- JPWO2021183917A5 JPWO2021183917A5 JP2022554893A JP2022554893A JPWO2021183917A5 JP WO2021183917 A5 JPWO2021183917 A5 JP WO2021183917A5 JP 2022554893 A JP2022554893 A JP 2022554893A JP 2022554893 A JP2022554893 A JP 2022554893A JP WO2021183917 A5 JPWO2021183917 A5 JP WO2021183917A5
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Claims (15)
- 少なくとも1つのコンピュータハードウェアプロセッサを使用して以下の工程を実行すること、を含む、少なくとも1つのコンピュータによって実行される方法であって、実行される工程が、
生体試料について発現データを得る工程であって、前記生体試料は対象から事前に得られており、前記発現データは各々の複数の細胞型に関連する複数の遺伝子のセットに関連する発現データであって、当該複数の細胞型のうちの第1の細胞型に関連する第1の遺伝子のセットに関連する第1の発現データを含む発現データを含む、工程と、
前記複数の遺伝子セットに関連する前記発現データと、第1の非線形回帰モデルを含む複数の非線形回帰モデルとを使用して前記第1の細胞型について第1の細胞構成比率を含む、前記複数の細胞型について複数の細胞構成比率を決定する工程を含み、ここで、前記第1の細胞構成比率は前記生体試料における前記第1の細胞型の細胞の推定比率を示し、前記第1の細胞型について前記第1の細胞構成比率を含む、前記複数の細胞型について複数の細胞構成比率を決定する工程は、
前記複数の細胞型の各細胞型について、各々の細胞型についての前記細胞構成比率を決定するための前記複数の非線形回帰モデルのうちの各々の非線形回帰モデルを使用して、前記細胞型に関連する遺伝子のセットに関連する発現データを処理する工程であって、前記第1の発現データを前記第1の非線形回帰モデルによって処理して、前記第1の細胞型について前記第1の細胞構成比率を決定する工程、及び
前記第1の細胞構成比率を出力する工程
を含み、
異なる非線形回帰モデルが、異なる細胞型についての細胞構成比率を決定するために使用され、前記非線形回帰モデルの各々が、前記複数の細胞型のうちの特定の各々の細胞構成比率を推定するために訓練されている、方法。 - 前記発現データが、
以下の遺伝子:ADAP2, ADGRE3, ADGRG3, ADORA3, AIF1, AOAH, APOBEC3D, ARHGAP15, ARHGAP30, ARHGAP9, ARHGDIB, BANK1, BLK, C1QA, C1QC, C3AR1, C5AR1, CAMK4, CBLB, CCDC69, CCL5, CCL7, CCR1, CCR2, CCR3, CD14, CD160, CD163, CD19, CD1D, CD2, CD22, CD226, CD244, CD247, CD27, CD300A, CD300C, CD300E, CD300LB, CD302, CD33, CD37, CD3D, CD3E, CD3G, CD4, CD48, CD5, CD53, CD6, CD68, CD69, CD7, CD79A, CD79B, CD86, CEACAM8, CECR1, CELF2, CLDND2, CLEC17A, CLEC2D, CLEC5A, CLEC7A, CMKLR1, CORO1A, CPNE5, CR2, CSF1R, CSF2RA, CSF3R, CTSS, CTSW, CXCR1, CXCR2, CXCR5, CYBB, CYFIP2, CYTH4, CYTIP, DENND1C, DERL3, DOCK2, EAF2, ELF1, ELMO1, EVI2B, FAM129C, FAM78A, FCER1G, FCGR1A, FCGR1B, FCGR2A, FCGR3B, FCMR, FCN1, FCRL1, FCRL2, FCRL3, FCRL5, FCRLA, FERMT3, FFAR2, FGR, FKBP11, FLT3LG, FMNL1, FNBP1, FPR1, FPR2, FPR3, GLCCI1, GLT1D1, GPR174, GZMM, HCK, HCLS1, HLA-DOB, HMHA1, ICAM3, IFI30, IFITM2, IGFLR1, IGHG1, IGHG3, IGHM, IGKC, IGLL5, IKZF1, IKZF3, IL10, IL16, IL2RB, IL2RG, IL4I1, INPP5D, IRF5, ITGAL, ITGAX, ITGB2, ITGB7, ITK, KCNA3, KCNAB2, KCNJ15, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DS2, KIR3DL1, KIR3DL2, KLRB1, KLRC2, KLRC3, KLRD1, KLRF1, KLRK1, LAG3, LAIR1, LAPTM5, LAT, LAX1, LCK, LCP1, LIM2, LRRC25, LSP1, LTA, LY9, MAP4K1, MEFV, MMP25, MNDA, MRC1, MS4A1, MS4A4A, MS4A6A, MSR1, MYO1F, MYO1G, MZB1, NCAM1, NCF2, NCKAP1L, NCR1, NCR3, NFATC2, NKG7, NLRC3, NMUR1, P2RY10, P2RY13, P2RY8, PADI2, PADI4, PARVG, PAX5, PGLYRP1, PHOSPHO1, PIK3AP1, PILRA, PLA2G7, PLCB2, POU2AF1, PPP1R16B, PRF1, PRKCB, PTGDR, PTPN22, PTPN6, PTPRC, PTPRCAP, PVRIG, PYHIN1, RAB7B, RAC2, RASGRP1, RASGRP2, RASGRP4, RASSF5, RCSD1, RHOH, RLTPR, S1PR5, SAMD3, SAMSN1, SASH3, SEC11C, SH2D1B, SIGLEC1, SIGLEC5, SIGLEC7, SIGLEC9, SIRPB2, SIRPG, SIT1, SLA2, SLAMF6, SNX20, SP140, SPI1, SPIB, SPN, SSR4, STAP1, STAT5A, STK4, TAGAP, TBC1D10C, TBX21, TCF7, TESPA1, TLR2, TMC8, TMIGD2, TNFAIP8, TNFAIP8L2, TNFRSF10C, TNFRSF13B, TNFRSF13C, TNFRSF17, TRAC, TRAF3IP3, TRAT1, TRBC2, TRDC, TREM2, TRGC1, TRGC2, TXNDC11, TXNDC5, TYROBP, UBASH3A, VAV1, VNN2, VNN3, VPREB3, VSIG4, WAS, XCL2, ZBED2を含む、免疫細胞に関連する遺伝子の群;
以下の遺伝子:BANK1, BLK, CD19, CD22, CD37, CD79A, CD79B, CLEC17A, CPNE5, CR2, CXCR5, DERL3, EAF2, FAM129C, FCRL1, FCRL2, FCRL3, FCRL5, FCRLA, FKBP11, GLCCI1, HLA-DOB, IGHG1, IGHG3, IGHM, IGKC, IGLL5, MS4A1, MZB1, PAX5, POU2AF1, SEC11C, SPIB, SSR4, STAP1, TNFRSF13B, TNFRSF13C, TNFRSF17, TXNDC11, TXNDC5, VPREB3を含む、B細胞に関連する遺伝子の群;
以下の遺伝子:BANK1, BLK, CD19, CD22, CD37, CD79A, CD79B, CLEC17A, CPNE5, CR2, DERL3, EAF2, FAM129C, FCRL1, FCRL2, FCRL3, FCRL5, FCRLA, FKBP11, GLCCI1, HLA-DOB, IGHG1, IGHG3, IGHM, IGKC, IGLL5, MZB1, POU2AF1, SEC11C, SPIB, SSR4, STAP1, TNFRSF13B, TNFRSF13C, TNFRSF17, TXNDC11, TXNDC5を含む、プラズマB細胞に関連する遺伝子の群;
以下の遺伝子:ADAM28, BANK1, BCL11A, BLK, CD19, CD22, CD37, CD72, CD79A, CD79B, CLEC17A, CPNE5, CR2, CXCR5, FAM129C, FCER2, FCRL1, FCRL2, FCRL3, FCRL5, FCRLA, HLA-DOB, MS4A1, PAX5, POU2AF1, RALGPS2, SPIB, STAP1, TNFRSF13B, TNFRSF13C, VPREB3を含む、非プラズマB細胞に関連する遺伝子の群;
以下の遺伝子:CAMK4, CBLB, CD2, CD226, CD3D, CD3E, CD3G, CD48, CD5, CD6, CD7, FLT3LG, ITK, KCNA3, KLRB1, LAG3, LAT, LCK, LTA, SIRPG, SIT1, SLA2, TBX21, TCF7, TESPA1, TRAC, TRAF3IP3, TRAT1, TRBC2, TRDC, TRGC1, TRGC2, UBASH3A, ZBED2;
a group of genes associated with CD4 T cells comprising the following genes: ANKRD55, CCR4, CD2, CD27, CD28, CD3D, CD3E, CD3G, CD4, CD40LG, CD5, CD6, FHIT, FLT3LG, ICOS, IKZF1, IL2RA, IL9, IRF4, ITK, LCK, LEF1, LTA, TESPA1, TNFRSF4, TRAC, TRAT1, TRBC2, UBASH3Aを含む、T細胞に関連する遺伝子の群;
以下の遺伝子:CCR4, CCR8, CD2, CD27, CD4, CTLA4, ENTPD1, FOXP3, HAVCR2, IKZF2, IKZF4, IL21R, IL2RA, IL2RB, IL2RG, ITGAE, ITK, LAG3, LTB, SIRPG, TIGIT, TNFRSF18, TNFRSF4, TNFRSF8, TNFRSF9, TRACを含む、制御性T細胞に関連する遺伝子の群;
以下の遺伝子:ANKRD55, CD2, CD28, CD40LG, CD5, CD6, FHIT, FLT3LG, IL7R, ITK, ITM2A, KLRB1, LCK, LEF1, LRRN3, NELL2, P2RY8, TCF7, TESPA1, THEMIS, TRAF3IP3, TRAT1を含む、ヘルパーT細胞に関連する遺伝子の群;
以下の遺伝子: CCL5, CD2, CD3D, CD3E, CD3G, CD6, CD7, CD8A, CD8B, CD96, CRTAM, CXCR3, EOMES, FCRL6, FLT3LG, GZMA, GZMB, GZMH, GZMK, ITK, KLRC2, KLRC4, KLRK1, PRF1, PRKCQ, PTGDR, PVRIG, SH2D1A, TBX21, TCF7, THEMIS, TIGIT, TRAC, TRAT1, TRBC2, UBASH3A, XCL2, ZAP70, ZBED2を含む、CD8 T細胞に関連する遺伝子の群;
以下の遺伝子:CCR7, CD160, CD28, CD5, CD8A, CD8B, CRTAM, EOMES, FCRL6, FGFBP2, GZMK, GZMM, IL7R, KCNA3, KLRF1, KLRG1, KLRK1, PRKCQ, PTGDR, PVRIG, S1PR5, SH2D1A, TCF7, ZAP70を含む、CD8 PD1 low T細胞に関連する遺伝子の群;
以下の遺伝子: CBLB, CD2, CD226, CD244, CD27, CD38, CD8A, CD8B, CRTAM, CTLA4, ENTPD1, FASLG, HAVCR2, ICOS, IL2RA, IL2RB, IRF4, ITGAE, KLRC1, KLRK1, LAG3, LTA, PDCD1, PRDM1, PRKCQ, PVRIG, SH2D1A, SIRPG, TIGIT, TMIGD2, TNFRSF9を含む、CD8 PD1 high T細胞に関連する遺伝子の群;
以下の遺伝子:CCL5, CD160, CD244, CD247, CD7, CLDND2, CTSW, GZMM, IL2RB, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DS2, KIR3DL1, KIR3DL2, KLRB1, KLRC2, KLRC3, KLRD1, KLRF1, KLRK1, LIM2, NCAM1, NCR1, NCR3, NKG7, NMUR1, PRF1, PTGDR, PYHIN1, S1PR5, SAMD3, SH2D1B, TMIGD2, XCL2を含む、NK細胞に関連する遺伝子の群;
以下の遺伝子:AOAH, CCR1, CCR2, CD1D, CD300C, CD300E, CD300LB, CD302, CD33, CECR1, CSF1R, CTSS, CYBB, FCN1, IRF5, MEFV, MS4A6A, PADI4を含む、単球に関連する遺伝子の群;
以下の遺伝子:ADAP ADORA3, C1QA, C1QC, C3AR1, C5AR1, CCL7, CCR1, CD14, CD163, CD33, CD4, CD68, CLEC5A, CMKLR1, CSF1R, CYBB, FPR3, IL10, IL4I1, MRC1, MS4A4A, MS4A7, MSR1, PLA2G7, RAB7B, SIGLEC1, TREM2, VSIG4を含む、マクロファージに関連する遺伝子の群;
以下の遺伝子:C15orf48, C1QC, C3AR1, CCL3, CCL3L3, CCL4L2, CCL7, CD14, CD68, CLEC5A, CSF1R, CXCL3, CYBB, GADD45G, GRAMD1A, IL10, IL12B, IL15RA, IL1RN, IL27, IL4I1, LILRB4, MMP19, PFKFB3, PLA2G7, SIGLEC1, SLAMF7, SOCS3, SOD2, SPHK1, TNF, TNFAIP6, TNIP3, VSIG4を含む、M1マクロファージに関連する遺伝子の群;
以下の遺伝子:ADAP2, C1QC, CCR1, CD14, CD163, CD209, CD4, CD68, CLEC5A, CMKLR1, CSF1R, CYBB, FKBP15, FPR3, GPNMB, LACC1, LIPA, MRC1, MS4A4A, MSR1, NPL, PLA2G7, RAB42, SIGLEC1, SLC38A6, STAB1, TREM2, VSIG4を含む、M2マクロファージに関連する遺伝子の群;
以下の遺伝子:ADGRE3, ADGRG3, C5AR1, CCR3, CEACAM8, CLEC7A, CSF3R, CXCR1, CXCR2, EVI2B, FCGR2A, FCGR3B, FFAR2, FPR1, FPR2, GLT1D1, IFITM2, KCNJ15, LILRB3, MEFV, MMP25, MNDA, P2RY13, PADI2, PADI4, PGLYRP1, PHOSPHO1, RASGRP4, SIGLEC5, TNFRSF10C, VNN2, VNN3, WASを含む、好中球に関連する遺伝子の群;
以下の遺伝子:ACTA2, ADAMTS2, CD248, COL16A1, COL1A1, COL1A2, COL3A1, COL4A1, COL5A1, COL6A1, COL6A2, COL6A3, FAP, FBLN2, FBN1, FGF2, LOXL1, MFAP5, PCOLCE, PDGFRA, PDGFRB, TAGLN, THBS2, THY1, VEGFCを含む、線維芽細胞に関連する遺伝子の群;
以下の細胞:ANGPT2, APLN, CDH5, CLEC14A, ECSCR, EMCN, ENG, ESAM, ESM1, FLT1, HHIP, KDR, MMRN1, MMRN2, NOS3, PECAM1, PTPRB, RASIP1, ROBO4, SELE, TEK, TIE1, VWFを含む、内皮細胞に関連する遺伝子の群;
以下の遺伝子:ACRBP, ADAP2, ADGRE2, ADGRE3, ADGRG3, ADORA3, AIF1, AOAH, C1QA, C1QC, C3AR1, C5AR1, CCL7, CCR1, CCR2, CCR3, CD14, CD163, CD1D, CD300A, CD300C, CD300E, CD300LB, CD302, CD33, CD4, CD68, CD86, CEACAM8, CECR1, CLEC5A, CLEC7A, CMKLR1, CSF1R, CSF2RA, CSF3R, CTSS, CXCR1, CXCR2, CYBB, EMILIN2, EVI2B, FCER1G, FCGR1A, FCGR1B, FCGR2A, FCGR3B, FCN1, FFAR2, FGL2, FPR1, FPR2, FPR3, GLT1D1, HCK, HK3, IFI30, IFITM2, IGSF6, IL10, IL4I1, IRF5, ITGAM, ITGAX, KCNJ15, LILRA3, LILRA5, LILRA6, LILRB2, LRRC25, LYN, LYZ, MAFB, MEFV, MMP25, MNDA, MPP1, MRC1, MS4A4A, MS4A6A, MSR1, NCF2, NINJ1, OSCAR, P2RX1, P2RY13, PADI2, PADI4, PGLYRP1, PHOSPHO1, PILRA, PLA2G7, PLEK, PRKCD, PSAP, RAB7B, RASGRP4, RNASE6, RP2, SIGLEC1, SIGLEC14, SIGLEC5, SIGLEC9, SIRPB2, SPI1, STX11, TLR2, TNFRSF10C, TNFSF13, TREM2, TYROBP, VNN2, VNN3, VSIG4, WASを含む、骨髄細胞に関連する遺伝子の群;
以下の遺伝子:CAP1, ANXA2R, APOBEC3D, APOBEC3G, BANK1, BLK, CAMK4, CARD11, CBLB, CCL5, CD160, CD19, CD2, CD22, CD226, CD244, CD247, CD27, CD37, CD3D, CD3E, CD3G, CD48, CD5, CD6, CD69, CD7, CD79A, CD79B, CLDND2, CLEC17A, CLEC2D, CPNE5, CR2, CTSW, CXCR5, CYFIP2, DEF6, DERL3, EAF2, ETS1, EVL, FAM129C, FCMR, FCRL1, FCRL2, FCRL3, FCRL5, FCRLA, FKBP11, FLT3LG, GLCCI1, GPR174, GPR18, GRAP2, GZMM, HLA-DOB, IGHG1, IGHG3, IGHM, IGKC, IGLL5, IKZF1, IKZF3, IL16, IL2RB, IL2RG, ITGB7, ITK, KCNA3, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DS2, KIR3DL1, KIR3DL2, KLRB1, KLRC2, KLRC3, KLRD1, KLRF1, KLRK1, LAG3, LAT, LAX1, LCK, LIM2, LTA, LY9, MAP4K1, MS4A1, MZB1, NCAM1, NCR1, NCR3, NFATC2, NKG7, NLRC3, NMUR1, P2RY10, P2RY8, PARP15, PAX5, PIK3IP1, POU2AF1, PPP1R16B, PPP3CC, PRF1, PTGDR, PTPRCAP, PVRIG, PYHIN1, RASAL3, RASGRP1, RASGRP2, RHOH, RLTPR, S1PR5, SAMD3, SEC11C, SH2D1B, SIRPG, SIT1, SKAP1, SLA2, SLAMF6, SP140, SPIB, SSR4, STAP1, TBC1D10C, TBX21, TCF7, TESPA1, TMC6, TMC8, TMIGD2, TNFRSF13B, TNFRSF13C, TNFRSF17, TRAC, TRAF3IP3, TRAT1, TRBC2, TRDC, TRGC1, TRGC2, TXNDC11, TXNDC5, UBASH3A, VPREB3, XCL2, ZBED2, ZNF101を含む、リンパ球に関連する遺伝子の群、
から選択される、第1の細胞型に関連する第1の遺伝子の群から選択される少なくとも10個の遺伝子についての発現データを含む、請求項1に記載の方法。 - 前記対象は、がんを有する、がんを有する疑いがある、又はがんを有するリスクがあり、そして/あるいは、前記発現データは、RNA発現データである、請求項1又は2に記載の方法。
- 前記第1の発現データを前記第1の非線形回帰モデルによって処理する工程は、
前記第1の非線形回帰モデルへの入力として前記第1の発現データを提供して、前記第1の細胞型からのRNAの推定比率を表す対応する出力を得る工程と、
前記第1の細胞型からのRNAの前記推定比率に基づいて、前記第1の細胞型について前記第1の細胞構成比率を決定する工程と
を含む、請求項1~3のいずれか一項に記載の方法。 - 前記発現データは、前記第1の細胞型に関連する前記第1の遺伝子のセットに関連する第2の発現データを含み、
前記第1の非線形回帰モデルは、
前記第1の発現データを入力として使用して、前記第1の細胞型からのRNAの前記推定比率についての第1の値を生成するように構成された第1のサブモデルと、
第2の発現データと前記第1の細胞型からのRNAの前記推定比率についての前記第1の値とを入力として使用して、前記第1の細胞型からのRNAの前記推定比率についての第2の値を生成するように構成された第2のサブモデルと
を含む、請求項1~4のいずれか一項に記載の方法。 - 前記発現データは、前記第1の細胞型とは異なる第2の細胞型に関連する第2の遺伝子のセットに関連する第2の発現データを含み、
前記1つ又は複数の非線形回帰モデルは第2の非線形回帰モデルを含み、
前記方法は、少なくとも一部には、前記第2の細胞型について第2の細胞構成比率を決定するために前記第2の発現データを前記第2の非線形回帰モデルによって処理することによって、前記第2の細胞型について前記第2の細胞構成比率を決定する工程を更に含む、
請求項1~5のいずれか一項に記載の方法。 - 前記第1の細胞型は、B細胞、CD4+ T細胞、CD8+ T細胞、内皮細胞、線維芽細胞、リンパ球、マクロファージ、単球、NK細胞、好中球、及びT細胞からなる群から選択される、請求項1~6のいずれか一項に記載の方法。
- 前記複数の遺伝子セットにおける遺伝子は、請求項2における遺伝子の群から選択される少なくとも25個、少なくとも35個、請求項50個、少なくとも75個、又は少なくとも100個の遺伝子を含み、前記複数の細胞構成比率を決定する工程は、前記少なくとも25個、少なくとも35個、請求項50個、少なくとも75個、又は少なくとも100個の遺伝子について発現データを処理する工程を含み、そして/あるいは
前記発現データは、前記第1の細胞型とは異なる第2の細胞型に関連する第2の遺伝子のセットに関連する第2の発現データを含み、第2の発現データは、請求項2における第2の遺伝子の群から選択される少なくとも10個の遺伝子についてのRNA発現データを含み、第2の細胞型が、B細胞、CD4+ T細胞、CD8+ T細胞、内皮細胞、線維芽細胞、リンパ球、マクロファージ、単球、NK細胞、好中球、及びT細胞からなる群から選択される、請求項2~7のいずれか一項に記載の方法。 - 前記1つ又は複数の非線形回帰モデルは、1つ又は複数のランダムフォレスト回帰モデルを含み、そして/あるいは、前記1つ又は複数の非線形回帰モデルは、1つ又は複数のニューラルネットワーク回帰モデルを含み。そして/あるいは、前記1つ又は複数の非線形回帰モデルは、1つ又は複数のサポートベクターマシン回帰モデルを含む、請求項1~8のいずれか一項に記載の方法。
- 前記第1の非線形回帰モデルは、少なくとも一部には、
シミュレートされた発現データを得る工程と、
前記シミュレートされた発現データを使用して、前記第1の非線形回帰モデルを訓練する工程と
によって訓練されており、そして/あるいは
前記第1の非線形回帰モデルは、
シミュレートされたRNA発現データを含む訓練データを得る工程であって、前記シミュレートされたRNA発現データは、前記第1の細胞型に関連する前記第1の遺伝子のセットについての第1のRNA発現データを含む、工程と、
前記第1の細胞型からのRNAの比率を推定するために前記第1の非線形回帰モデルを訓練する工程であって、
前記第1の非線形回帰モデル及び前記第1のRNA発現データを使用して、前記第1の細胞型からのRNAの推定比率を生成する工程、及び
前記第1の細胞型からのRNAの前記推定比率を使用して、前記第1の非線形回帰モデルのパラメーターをアップデートする工程
を含む、訓練する工程とによって訓練されており、そして/あるいは
前記第1の非線形モデルは、シミュレートされた発現データを得ることによって少なくとも部分的に訓練されたものであり、シミュレートされたデータを得ることは、複数の細胞型のサンプルからのRNA発現データを所定の割合で組み合わせることによって複数の人工的混合物を得る工程、ここで、任意選択で、シミュレートされた発現データは、シミュレートされた悪性細胞RNA発現データを含み、シミュレートされたデータを得ることは、得られた発現データにランダムな過剰発現ノイズを加えることを含む;
シミュレートされた発現データを使用して、第1の非線形回帰モデルを訓練する工程、
を含む、請求項1~9のいずれか一項に記載の方法。 - 前記シミュレートされた発現データを得る工程と、
前記シミュレートされた発現データを使用して、前記第1の非線形回帰モデルを訓練する工程と
を更に含む、請求項10に記載の方法。 - 前記シミュレートされた発現データを得る工程は、前記シミュレートされた発現データを生成する工程を含み、前記シミュレートされた発現データを生成する工程は、
1つ又は複数の生体試料からRNA発現データのセットを得る工程であって、前記RNA発現データのセットは微小環境細胞発現データ及び悪性細胞発現データを含む、工程と、
前記微小環境細胞発現データを使用して、シミュレートされた微小環境細胞発現データを生成する工程と、
前記悪性細胞発現データを使用して、シミュレートされた悪性細胞発現データを生成する工程と、
前記シミュレートされた微小環境細胞発現データと前記シミュレートされた悪性細胞発現データとを組み合わせて、前記シミュレートされた発現データの少なくとも一部を作成する工程と
を含む、請求項11に記載の方法。 - 前記第1の細胞型についての発現プロファイル及び前記第1の細胞型についての前記第1の細胞構成比率を使用して、悪性腫瘍発現プロファイルを決定する工程、
を更に含む、請求項1~12のいずれか一項に記載の方法。 - 少なくとも1つのハードウェアプロセッサと、
前記少なくとも1つのハードウェアプロセッサによって実行されると、前記少なくとも1つのハードウェアプロセッサに、請求項1~13のいずれか一項に記載の方法を実施させるプロセッサ実行可能命令を格納する少なくとも1つの非一時的なコンピュータ読取り可能な記憶媒体と
を含むシステム。 - 少なくとも1つのハードウェアプロセッサによって実行されると、前記少なくとも1つのハードウェアプロセッサに、請求項1~13のいずれか一項に記載の方法を実施させるプロセッサ実行可能命令を格納する少なくとも1つの非一時的なコンピュータ読取り可能な記憶媒体。
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