Manuscript Detail

Title: Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells

Authors: Kusnadi, Anthony et al

Abstract: The molecular properties of CD8(+) T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8(+) T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8(+) T cell response to SARS-CoV-2 was ‘exhausted’ or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8(+) T cell memory responses in patients with severe COVID-19 illness. CD8(+) T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8(+) T cells responding to SARS-CoV-2.

Journal: Sci Immunol

Curator: Jane Wang

Reviewer: Aris Floratos

Author-provided data:

paper: Kusnadi, A., Ramírez-Suástegui, C., Fajardo, V., Chee, S. J., Meckiff, B. J., Simon, H., Pelosi, E., Seumois, G., Ay, F., Vijayanand, P. and Ottensmeier, C. H. (2021). Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells. Sci Immunol https://doi.org/10.1126/sciimmunol.abe4782
contributor: Pandurangan Vijayanand; Christian H. Ottensmeier
contributor_organization: La Jolla Institute for Immunology
contributor_email: vijay@lji.org; cottensmeier@lji.org

- description: Differentially expressed genes (adj. p value < 0.05 and LFC > 0.25) in SARS-CoV-2-reactive CD8+ T cells (from cluster 0 representing non-exhausted cells) when comparing severe vs. mild disease in acute COVID-19 infection.
- exact_source: Table S8, tab "A - Cluster 0". Link: https://immunology.sciencemag.org/highwire/filestream/644191/field_highwire_adjunct_files/10/abe4782_Table_S8.xlsx
- tissue: PBMC
- immune_exposure: SARS-CoV-2 infection
- cohort: The cohort consisted of 17 non-hospitalized patients with mild COVID-19 disease and 22 hospitalized patients with severe COVID-19 disease. The median age of the hospitalized patients was 60 (33-82) and 77% were male. The median age of the non-hospitalized participants was 39 (22-50) and 47% were male.
- comparison: SARS-CoV-2-reactive CD8+ T cells from COVID-19 patients with severe vs. mild disease
- repository_id: GSE153931
- platform: HGNC symbol
- response_components: RPS4Y1,ITM2A,DUSP4,CRTAM,CLDND1,MT2A,HLA-DRB1,LMNA,MYO1G,BCL2L1,SAMSN1,IL2RA,FGFBP2,CD96,LINC00944,WAS,BIRC3,CXCR4,EWSR1,SNHG15,AMICA1,ZFP36L1,AD000671.6,TNFRSF9,MIR4435-1HG,LPXN,DNAJC15,PIM2,MCL1,ACTA2,CD70,PHLDA1,CD6,SLA,GADD45B,SH2D2A,HMGA1,MIR155HG,REL,BHLHE40,MAP2K3,RNF114,GABARAPL1,PIM3,EIF1AY,HLA-DQA1,SF3B4,CNBP,MTHFD2,NONO,NFKB1,SUPT4H1,CMTM6,BCL2L11,SATB1,LYST,TNIP3,LITAF,EGR2,EIF4G2,CD83,WBP2,RBPJ,RHOG,TUBA1B,SRSF2,RP11-291B21.2,HLA-DPB1,PSMD5-AS1,ANP32E,ITM2C,DARS,FOXP1,SELT,DUSP10,CXorf40B,TNFAIP8,HNRNPK,PRDM1,DDB2,RPS27L,UBE2A,MAPK1IP1L,RABGGTB,ZFR,RGCC,ITGA1,DDX3Y,RELA,CHMP5,PRR14,EIF5,SF3A1,SERPINB9,UBE2B,PABPC1,TNFAIP3,BTG3,APBB1IP,CTLA4,MFSD10,NUP62,GPX4,HLA-DMA,YWHAE,PPP1R15A,LDHA,KPNA2,MCOLN2,DNAJA1,KXD1,YWHAQ,IRF4,LIMA1,PRR13,CD97,TOB1,KPNB1,FKBP1A,FAS,CLEC2D,FNDC9,SRGN,PSMD7,CTD-2020K17.1,CAPZA1,LAIR2,SDHD,ZNF267,UBC,UBASH3A,CACYBP,ISCU,MSMO1,CIRBP,KIF5B,RARG,TRAF1,HIST1H1C,DGUOK,MT1X,STAT5A,GORASP2,SNX6,STARD7,TANK,FDFT1,ATF4,JAKMIP1,SAP30BP,YARS,DUSP2,TRIM69,ARPC4,ABI1,CREM,IL21R,ATP1B3,SQRDL,MAT2B,CMC1,TUBA1C,NAB2,TXN,FDPS,CCNDBP1,SREBF2,POLR2K,SPPL2A,DHCR24,NR4A2,GNG4,HLA-DPA1,TSC22D3,ARL16,CASP1,AC017002.1,RAD21,PYHIN1,SERPINB6,PCNP,PSMB2,PSMB5,DDIT4,PRDX3,AKIRIN2,MRPL20,BLOC1S2,RANGAP1,HMGN2,SUB1,DTHD1,PSMF1,SAP18,NOP14,ZNRD1,CPSF7,EMD,CNOT7,PSMA6,ACAT2,SF3B2,LMNB1,PLK3,HMGCS1,BCL2A1,ADRM1,CCR7,ITGAL,VIM,NRBP1,SHISA5,HIF1A,WARS,CBLL1,SMAP2,C16orf13,LRMP,LSM14A,MT1E,TAGAP,DDX5,MVP,DHRS3,BAG6,SYTL3,CD44,ZEB2,SRP9,MRPL4,HMGB2,SDC4,RNF10,SMARCE1,FMNL1,RNF181,CCAR1,U2AF1L4,CASC3,NGRN,MOB1A,GLO1,ATP6V0C,TBC1D17,NFKBIA,CYCS,GATA3,PSMC2,PPP1R18,RSRC2,CCDC90B,HIST1H2AC,CYB5R3,SRM,NPTN,ZBTB38,CBR1,CBLB,SF3A2,PPDPF,HNRNPLL,KDELR2,TMEM123,C14orf1,QRICH1,ZFY,VAPA,SRSF3,TRIM22,SLMO2,PIGT,C7orf73,HIST1H1E,PSMD11,C11orf58,NDUFS2,TMBIM1,NDUFB5,RAB11A,DENND4A,PDCD10,KIF3A,MYADM,GRSF1,NAMPT,RP11-81H14.2,DPF2,ARHGEF2,CCNK,ZNF281,EXOSC3,H2AFZ,NFE2L2,MRPL37,NDUFA3,NR4A1,INPP5F,MRPL50,C7orf55-LUC7L2,KLRG1,SERTAD1,MT1F,JUN,EIF4A2,YPEL5,FAM96A,CPSF6,PLP2,PCNA,ARHGAP25,DUSP11,TNFSF4,ATF7IP,EPS15,RNF115,ZBED2,TROVE2,SFI1,ZNF410,MECP2,PRCC,SH3BGRL,STX5,CEP57,MRPS18C,SH3BP2,CARS,PQLC3,WBP11,PRKAR1A,COX17,KMT2A,NUP98,NUMA1,GGA2,NDUFS8,TECR,DIMT1,PQBP1,SNRPB2,ANXA11,EOMES,SLC1A5,UBLCP1,PSMD8,TMEM30A,NCL,GTF2H5,PTBP1,DESI1,C10orf128,TIMM17A,EBI3,LRRC41,SHFM1,MRFAP1,LEPROT,DAZAP2,MED15,MARCH7,CCDC115,NINJ1,BSG,KDM6B,INSIG1,RALGDS,CERS5,DDX24,IER2,KIAA1671,KLF10,KANSL1,UBE2I,PSMC6,KCNN4,CGGBP1,ILKAP,VCP,C7orf50,LCP2,TNIP1,BIRC2,SNHG12,SDCBP,CSRP1,PPP6C,EIF6,ATP5B,ALOX5AP,POLR2A,MAST3,ZNFX1,FASLG,SNRPN,SYNGR2,BRD2,CDCA4,MRPS18B,AKT2,IFNG,EED,ZNF580,C21orf91,TGIF1,AKIRIN1,PTP4A1,RNF149,TNFSF9,CLK3,SLC3A2,CHMP1B,ZBTB1,SNX11,YIPF4,RHBDD2,PPT1,MDH2,PRDX6
- response_behavior: up
  - - description: Differentially expressed genes (adj. p value < 0.05 and LFC > 0.25) in SARS-CoV-2-reactive CD8+ T cells (from cluster 1 representing exhausted cells) when comparing severe vs. mild disease in acute COVID-19 infection.
    - exact_source: Table S8, tab "B - Cluster 1". Link: https://immunology.sciencemag.org/highwire/filestream/644191/field_highwire_adjunct_files/10/abe4782_Table_S8.xlsx
    - tissue: PBMC
    - immune_exposure: SARS-CoV-2 infection
    - cohort: The cohort consisted of 17 non-hospitalized patients with mild COVID-19 disease and 22 hospitalized patients with severe COVID-19 disease. The median age of the hospitalized patients was 60 (33-82) and 77% were male. The median age of the non-hospitalized participants was 39 (22-50) and 47% were male.
    - comparison: SARS-CoV-2-reactive CD8+ T cells from COVID-19 patients with severe vs. mild disease
    - repository_id: GSE153931
    - platform: HGNC symbol
    - response_components: RPS4Y1,WAS,TUBA1C,GNLY,PHLDA1,TUBA1B,LTB,LTA,LAG3,ALOX5AP,GZMB,CCL3,EWSR1,EIF1AY,GZMH,SF3B4,LCP2,STIP1,FASLG,SH2D2A,BCL7C,CCL4,WARS,CD6,CD97,CD8A,NONO,ZYX,NUP62,PPP1R18,RELA,ZFP36L1,CSF2,PIM1,MAPK1IP1L,VASP,SELT,HMGA1,MCL1,C10orf128,MAP2K3,IER3,SRM,ITGA4,PTMS,CISH,SLC1A5,SF1,BCL2L1,CYB5R3,NFKBIA,SHISA5,ITM2A,ATP1B3,DDX3Y,TNF,IL2RB,GATA3,GNB2,NDFIP2,CHCHD10,PDE4A,WBP2,KXD1,BHLHE40,MYADM,SDF4,DOK2,SH3BP1,TNFRSF18,DUSP1,ARF6,SFPQ,MT-ATP8,SLC9A3R1,PPP1R15A,IL2RA,ARRB2,LIM2,NFAT5,SF3A2,BAG6,FOS,ZFP36,ARHGEF1,ODC1,TUBA4A,PTBP1,EIF4G2,YWHAH,ITGB7,TNFRSF1B,RBMX,YARS,CITED2,ABI3,CPSF6,MAP7D1,SF3A1,CYBA,KLRG1,LAMP1,SOCS1,CAMTA2,PIM3,GYPC,MAPKAPK3,NUTF2,TNFRSF9,PTPN7,MRPL4,PRR14,JUNB,JAKMIP1,UPP1,RNF187,LPXN,APBB1IP,RASAL3,SF3B2,ACTN4,FXYD5,CS,GMIP,NOLC1,FMNL1,RNPS1,ZFP36L2,CPSF7,HNRNPH1,PBX4,HNRNPAB,HNRNPK,UBAP2L,TCERG1,CD69,CISD3,AKT2,IFI6,CD68,H2AFY,RP11-345J4.5,FKBP4,SATB1,RAD23B,NFKB2,CD7,SNRNP70,ACAA2,AK2,GORASP2,TBX21,MED15,STX3,YBX1,CLPTM1,EAF1,QRICH1,FAM3C,FLOT1,ELAVL1,EGR2,WDR1,LRP10,HSF1,RRAS2,SYNGR2,DAZAP1,KHDRBS1,H2AFX,SRSF2,MRPS6,PNP,CBLL1,SNX10,SURF4,ANXA11,MIR155HG,CCND3,ZFR,PSMD3,FEZ1,SASH3,ADRM1,HIST1H1E,PDLIM2,PRR13,FLT3LG,CXCR3,SCAF4,TNFRSF1A,RALGDS,ARL2,EOMES,DCTPP1,CBFB,RGS16,S1PR5,RASSF5,SAMSN1,SLC43A3,MYBL1,IVNS1ABP,NOP16,RGS3,NDUFA6,P4HB,NAA20,FERMT3,RPIA,CDC37,SMARCA4,SYNGR1,DEF6,LYST,DHCR24,TSPAN17,KLRD1,CYC1,BTG1,NDUFS8,HNRNPUL1,TAF9,IFI44L,PSMC4,FARSA,RAB8A,TAGLN2,ACTN1,DIMT1,PRCC,R3HDM4,RBM42,ETS1,EIF5,SRRT,TMEM189,E2F4,SS18,TBC1D10C,TPM4,TGFB1,APOBEC3G,SNHG7,MYO1G,TIMM10,SRPK2,UTY,ARHGAP9,RELB,HIGD1A,ZFY,NFATC3,RNF10,DAD1,PLK3,ARHGEF2,TUFM,CST3,ATAD3B,FKBP11,IDH2,SNX9,PPDPF,PCSK1N,ABI1,FHOD1,ATP2A3,MRPL12,RABGGTB,CYFIP2,QSOX1,AHCY,TOMM40,HNRNPA0,CHPF,CEBPB,SAP30BP,SELPLG,TERF2IP,C19orf24,TMEM248,MVD,BSG,FKBP1A,SLC39A8,WIPF1,ATP6V0C,PNPLA2,ELK1,PCNP,DUSP10,GGA2,SLC3A2,PIGT,TESPA1,HDGFRP3,CNOT3,MARS,IMPDH2,CCDC86,SEMA4D,FAM195A,TPGS1,SYVN1,UBE2I,GOT2,BOP1,ATXN2L,RBMS1,TNFRSF4,RNF44,PABPC4,ATF5,SERPINB9,RNF40,ICAM1,CXCR6,JUND,GRINA,CCDC97,TICAM1,POLD2,SREBF2,RBPJ,SRRM2,SAP18,SNRPD1,PUF60,RP11-81H14.2,PPM1M,FASN,FBRS,TTTY15,PRDM1,KPNA2,RALY,PTP4A1,RTN4,PML,APEX1,MRPL20,FAM50A,RNF11,PCBP2,ATIC,STRA13,SOCS2,MYC,IFRD2,PDCD2,KPNB1,C20orf24,CLPP,IARS,TMC6,SHMT2,NIFK,RAVER1,ZFAND5,GRWD1,LSM4,GLIPR2,POLDIP2,EML2,PABPC1,CCNK,CARD11,CD8B,TMEM43,COMT,RIN3,TRABD,ETFA,SCAMP4,MAP3K11,AGFG2,ACSL5,CLTB,MSN,CD55,ARSA,RAP1A,MATK,TRAP1,ILKAP,TUBA1A,PFN1,ARMC10,ACLY,AIMP2,MLF2,GGA3,GPR141,VCP,MT-CO1,GART,YWHAQ,TAF6,LAGE3,PRDX2,S1PR4,PRRC2A,RAB7A,WBP11,HGS,MZT2A,CRTC2,AHSA1,MT-ATP6,EXOSC4,RANGRF,CIRH1A,FPGS,CD63,SLC39A6,TEX30,FLNA,SP2,TSC22D3,TMEM256-PLSCR3,HLA-DQB1,DUSP5,CYCS,EVL,STARD7,TMBIM1,MRTO4,APOL3,XBP1,COMMD7,CD300A,CSRNP1,CCT4,DTX2,ATP5G3,SCAF1,ALKBH6,TYMP,STRAP,DESI1,RHOF,COA4,TXN,YIF1A,DCXR,NFKB1,TOMM70A,CCR5,LRRC47,CBLB,GFI1,UBE2V1,C9orf16,UFC1,NPTN,SMG9,STT3A,DIAPH1,ZNF593,GSPT1,SLC10A3,ARL4A,SF3B3,ATP13A1,DNTTIP2,CRYZ,ILF3,RRP9,VARS,NOP10,CADM1,CMTM3,GDI1,PFDN2,HAVCR2,KEAP1,C6orf136,PRF1,PRELID1,ARHGAP17,UBE2L3,ACTG1,MON1B,TNIP2,GTF3A,GPATCH4,CHERP,SPN,APOA1BP,EEF1E1,NUP98,OGFR,SLC7A5,LSM14A,SIT1,KCNAB2,PRSS21,BRPF1,ATG4D,ASXL1,PTGER2,SRSF3,SLC25A33,NABP2,DHRS3,UBR4,CD72,PKM,U2AF2,ARPC5L,ATAD3A,PTDSS1,NDUFAF4,SSBP4,MED25,LAIR1,UBQLN1,ETF1,SRP9,HSPA9,SMPD4,HMHA1,CHMP5,PDIA6,CRLS1,DDB1,NSUN2,RUVBL2,ZFAND3,SRSF10,AURKAIP1,ACADM,PRMT1,ALAS1,TMC8,DHCR7,GCH1,GET4,SPINT1,PARVG,GRSF1,LETM1,LILRB1,CCND2,IER2,NT5C,EMD,NSG1,DAZAP2,TMEM147,CHD1L,WDR77,DUSP23,PTOV1,ADAP1,SSU72,EIF5A,USP39,CD58,GLUD1,NOC4L,STOML2,PPP5C,RANBP1,MPHOSPH6,OGDH,CCDC124,GSTP1,CES2,BCL2A1,SEC24B,NELFA,GTF2E2,GRK6,HRASLS2,C8orf88,EIF2S1,RHOB,C10orf54,ISG20L2,KDELR2,LATS1,ZDHHC3,DUSP2,SARS,DNAJC1,GUCD1,PHB,KDM5D,PPP4C,FAM49A,MKNK1,MT-CO2,CMPK1,ADSL,HSPD1,SUPT4H1,IKBKG,PGP,ANXA6,TBC1D17,RARA,SUN2,RCE1,DDX27,PPP6R2,HNRNPL,FAM46C,AP2A1,ITGA1,GTF3C1,CASP1,PA2G4,POU2F2,HLA-F,SGK1,PSMB5,SLC25A22,SNHG12,NME1,TPRA1,THEMIS2,TMEM204,EIF4A2,DNM2,STUB1,PDCD5,PSTPIP1,SHC1,CD320,PPP1R11,PXN,SNX3,SLC52A2,BCL7B,DUSP4,LRRC41,ARF4,CCT2,CSNK1D,EMC10,DNPEP,CNN2,EDC4,TMUB1,VPS37B,MAP2K2,PSME3,NOP14,S100A11,PSMC2,BUD31,UBE2F,MTA2,PNPLA6,TCIRG1,RQCD1,GUSB,EHD1,PREX1,EBNA1BP2,TOMM34,NCLN,DBNL,PES1,YTHDF3,NOL11,CNIH1,ANKRD28,PSMC1,CANT1,SACM1L,IL15RA,TFDP1,CENPV,AKAP17A,GARS,PANK2,B3GAT3,PRKD2,SNF8,BAZ1B,DHPS,MED16,PRKAR1A,NFKBIB,OSBPL3,PHC3,PSMF1,IRF7,MAP1S,NENF,PCK2,IMP4,YWHAE,CAPRIN1,SZRD1,PREB,EIF4G1,DAP,UBE2A,NOP2,SERPINB1,UNC13D,GNPTAB,CD2BP2,FAM207A,RPS6KA1,NAA10,PPP1R10,ATPAF1,HSPB1,DCAF13,TESC,PUS1
    - response_behavior: up
      - description: Differentially expressed genes (adj. p value < 0.05 and LFC > 0.25) in SARS-CoV-2-reactive CD8+ T cells (from cluster 2 representing non-exhausted cells) when comparing severe vs. mild disease in acute COVID-19 infection.
        
        exact_source: Table S8, tab "C - Cluster 2". Link: https://immunology.sciencemag.org/highwire/filestream/644191/field_highwire_adjunct_files/10/abe4782_Table_S8.xlsx
        
        tissue: PBMC
        
        immune_exposure: SARS-CoV-2 infection
        
        cohort: The cohort consisted of 17 non-hospitalized patients with mild COVID-19 disease and 22 hospitalized patients with severe COVID-19 disease. The median age of the hospitalized patients was 60 (33-82) and 77% were male. The median age of the non-hospitalized participants was 39 (22-50) and 47% were male.
        
        comparison: SARS-CoV-2-reactive CD8+ T cells from COVID-19 patients with severe vs. mild disease
        
        repository_id: GSE153931
        
        platform: HGNC symbol
        
        response_components: RPS4Y1,CRTAM,CLDND1,LMNA,ITM2A,MT2A,CD70,DUSP4,C10orf128,HLA-DRB1,AMICA1,STMN1,DNAJC15,PCNA,CBR1,IRF4,MT1X,TNFAIP8,PIM2,LITAF,CMC1,LINC00944,LGALS3,ZBTB38,FGFBP2,SERPINB6,MCM7,CD96,TNIP3,MYO1G,ANP32E,MT-ATP8,ALOX5AP,ZNRD1,LMNB1,HLA-DQA1,KLRG1,PSMD5-AS1,RP11-1407O15.2,MCM5,BIRC3,TAGAP,SAMSN1,WAS,TYMS,CXCR4,REL,MTHFD2,EIF1AY,MIR4435-1HG,ZBED2,CD83,HLA-DQB1,HMGB2,CNBP,CMTM6,C7orf73,TRAT1,NFKB1,BCL2L1,LYST,C14orf1,ACTA2,LIMA1,FAS,PPP1R15A,KIF3A,EIF4A2,LPXN,NUP62,RABGGTB,RPA3,HLA-DPB1,MRPL15,STAT1,MCM2,DUSP2,MCL1,MIR155HG,TNFAIP3,YWHAQ,CD44,HMGCS1,SF3B4,HLA-DMA,RNF114,MCM6,BCL2L11,MRPL37,SLC38A5,CLEC2D,INPP4B,FOXP1,GABARAPL1,ARID5B,KPNA2,PRDM1,NUDT21,EIF4G2,GADD45B,CENPM,XCL2,NSMCE4A,SLC1A5,CACYBP,ATF7IP,PPDPF,AD000671.6,TRIM69,GINS2,SNHG15,RAD21,DDB2,TNFRSF14,BHLHE40,DPM2,STAT5A,CASP1,PSMB5,SNRNP25,EED,EWSR1,DHCR24,EXOC2,SRSF2,NEAT1,RAD50,DNAJA1,NAMPT,H2AFV,SHMT2,EMC6,HADH,NONO,DUT,LBH,SRGN,FOXN3,MCM3,WDR18,MCM4,C19orf48,HINT2,PPT1,INSIG1,SLC43A3,CEP57,ARL16,CHID1,H2AFZ,SUPT4H1,COPG2,C19orf24,PQLC3,MOB1A,MRPL50,SF3A1,UBL7,EGR2,EXOSC3,TNFRSF9,SH3BGRL,POLD2,RPS27L,C12orf75,TMEM167A,ITGA1,FEN1,SELT,MAPK1IP1L,MAT2B,SPAG7,IL2RA,UBE2T,MRPL16,ZDHHC12,CDCA4,EOMES,SDHD,MCOLN2,MT1F,SMC2,CASP3,NAA38,DESI1,GPX4,POLR3K,ZNF267,THOC3,DARS,CTD-2020K17.1,SIGMAR1,TIMMDC1,HBS1L,CTSA,SERPINB9,TMEM106C,HMGA1,NDUFB5,NUP37,PSMG2,NAP1L1,ACAT2,MRPL51,MAP2K3,PRPF38A,NDUFS8,PHGDH,DLD,SDC4,MT1E,FAM96A,MATR3,NFKBIA,CSRP1,SATB1,RPS10,TMEM97,KIF22,JUNB,DHRS4L2,SUB1,CENPK,SRSF3,SEPT2,KDELR1,SLC25A3,NSG1,SLBP,GLO1,NDUFS2,ERCC1,UNG,NIP7,EXOSC8,ATF4,CCR7,PTRHD1,BCL2L12,EIF4E,HMGCR,MDP1,AOAH,CKS1B,PELP1,PEX2,NOB1,EIF4EBP1,IL21R,HMBS,CXorf40B,WBP2,SF3A2,TMEM14A,TIAL1,PABPC1,IRF1,TANK,CLSPN,CENPU,TMPO,QRICH1,TRAF4,UROS,ESD,TMEM219,CSDE1,SH2D1A,EBI3,CRTAP,IL12RB2,RPS26,PAFAH1B3,IFI27L1,JAKMIP1,SQRDL,DSN1,SNRPD3,CPSF7,RQCD1,C6orf48,KCNN4,PRDX6,RBBP4,EPS15,ZNF622,RFC2,FNDC9,MAD2L1,RPP25L,MED28,GIMAP4,CCDC109B,ZNF410,COQ4,RDX,GMNN,VRK1,PCK2,CCNDBP1,DDX41,BTG3,HIF1A,DGUOK,LIM2,PDCD4,NDUFS4,TIFA,MSMO1,APEX1,CAPZA1,MRPL34,TCF19,C16orf80,DTHD1,COPS8,PIM3,CCDC167,SPPL2A,ZFP36L1,GSDMD,GSKIP,HNRNPA0,CHEK1,PIN4,AKIP1,LRPPRC,NRBP1,CD2BP2,NAP1L4,CCNK,LIG1,NSMCE1,PTCD3,SKA2,SNRPC,LAMTOR2,NDUFA5,CUEDC2,TMEM69,SREBF2,ALKBH7,MPHOSPH6,CTBS,ATP6V0E2,STARD7,EXOSC7,VPS29,DNAJA2,RNF115,NGRN,POLD1,TUBA1B,IFI16,TRIM26,HNRNPLL,HIF1AN,PRIM1,SMAD2,PCBD1,MYCBP,SPSB3,SNRPN,ZC3H7A,CDCA7,VRK3,SRM,CXorf40A,SUPT7L,TMEM230,IPO7,SS18,RELA,DERA,PHF5A,POLR2H,FANCL,KDELR2,ZNF706,FIS1,TTC38,TBP,MED16,ERH,YWHAE,GATA3,ETS2,PTTG1,CCNG1,TSN,FAM129A,PIGS,KXD1,NBN,CDKN2A,SSRP1,RPS29,CASC3,TRAFD1,NINJ1,ZFR,CD8B,ZFY,RP11-277P12.20,RAB7A,TRIM22,ACTR6,UBLCP1,TNFSF4,IDI1,GAMT,SCYL1,CAND1,KMT2A,PSIP1,ZWINT,SLC30A5,IMPDH2,POLR2G,AKIRIN1,MRPL10,NUDT8,FXR1,CALCOCO2,SNAP29,YEATS4,CNOT7,CTLA4,UBE2B,DHFR,ABHD5,FRG1,AZIN1,KIF5B,IL13,POLR2K,BCAP29,WDR75,NOL8,ADI1,GTF2H5,RBMX,MED6,C11orf58,CCDC28A,KIAA0101,ASF1B,LSM5,GTF2H2C
        
        response_behavior: up

Spreadsheet: Link to curation spreadsheet