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Lassa virus detection using gene expression analysis

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    Lassa virus detection using gene expression analysis Lassa virus detection using gene expression analysis Presentation Transcript

    • Lassa VirusDetection Using GeneExpression AnalysisMEEDIACVKDLVSKYLVDNERLSRQKLAFLVQTEPRMLLMEGLKLLSLCIEVDSCNANGCEHNSEDKSVERILHDHGILTPSLCLWYPDGYK RNA PolymeraseLTGNVLILLECFVRSSPANFEQKYIEDFKKLEQLKEDLKSVDINLIPLIDGRTSFYNEQIPDWVNDKLRDTLFSLLKYAQESNSLFEESEYSRLCESLFMTSGRLSGVESLNVLMDNRSNHYEEVIASCHQGINNKLTAHEVKLQIEEEYQVFRNRLRKGEIEGQFLKVDKSQLLNELNNLYADKVVAEDNIEHLIYQFKRASPILRFLYANVDEGNEKRGNQTIGECQVQCWRSFLNKVKSLRILNTRRKLLLIFDALILLASKHDLMKQKCLKGWLGSCFLRVKDRLVSLEATKRDLEKWGERGNRLRSRITQSSQCLSKNQILNSIFQKTILKATTALKDVGISVDHYKIDMEVICLNSYDLIMDFDVSGVVPTISYQRTEEETFPYVMGDVELLGTTDLERLSSLSLALVNSMKTSSTVKLRQNEFGPARYQVVRCKEAYCQEFSLGNTELQLIYQKTGECSKCYAINDNKVGEVCSFYADPKRYFPAIFSAEVLQTTISTMISWIEDCNELEGQLNNIRSLTKMILVLILAHPSKRSQKLLQNLRYFVMAYLSDYHHKDLIDKIREELITDVEFLLYRLIRTLMNLVLSEDVKSMMTNRFKFILNVSYMCHFITKETPDRLTDQIKCFEKFLEPKVRFGHVSTNPADTATEEELDDMVYNAKKFLSKDGCTTIEGPDYKRPGVSKKYLSLLTSSFNNGSLFKEREVKREIKDPLITSGSAALDLASKKSVVVNKYTDGSRILNYDFNKLTALAVSQLTEVFSRKGKYLLNKQDYEYKVQQAMSNLVLGSGQLKSDADGADLDEILLDGGASDYFDQLKETVEKIVDQYREPVKLGSGPNGDGQPSINDLDEIVSNKFYIRLIKGELSNHMVEEFDHDILPGKFYEEFCNAVYENSRLKQKYFYCGHMSQCPIGELTKAVSTRTYFNHEYFQCFKSILLIMNANTLMGRYTHYKSRNLNFKFDMGKLSDDVRISERESNSEALSKALSLTNCTTAMLKNLCFYSQESPQSYDSVGPDTGRLKFSLSYKEQVGGNRELYIGDLRTKMFTRLIEDYFEAISLQLSGSCLNNEKEFENAILSMKLNVSLAHVSYSMDHSKWGPMMCPFLFLTVLQNLIFLSKDLQADIKGRDYLSTLLMWHMHKMVEIPFNVVTAMMKSFIKAQLGLRKKTKQSITEDFFYSNFQAGVVPSHISSILDMGQGILHNTSDFYALISERFINYAISCICGGTIDAYTSSDDQISLFDQSLTELLQRDPEEFRTLIEFHYYMSDQLNKFVSPKSVIGRFVAEFKSRFFVWGDEVPLLTKFVAAALHNIKCKEPHQLAETIDTIIDQSVANGVPVHLCNLIQKRTLNPLQYARYPIDPFLLNCETDVRDWVDGNRSYRIMRQIEGLIPNACSKIRSMLRKLYNRLKTGQLHEEFTTNYLSSEHLSSLRNLCELLDVEPPSESDLEYSWLNLAAHHPLRMVLRQKIIYSGAVNLDDEKIPTIVKTIQNKLSSTFTRGAQKLLSEAINKSAFQSSIASGFVGLCRTLGSKCVRGPNKENLYIKSIQSLISDVKGIKLLTNSNGIQYWQVPLELRNGSGGESVVSYFRPLLWDYMCISLSTAIELGAWVLGEPKTVKVFDFFKHNPCDYFPLKPTASKLLEDRVGLNHIIHSLRRLYPSVFEKHILPFMSDLASTKMKWSPRIKFLDLCVALDVNCEALSLVSHIVKWKREEHYIVLSSELRLSHSRTHEPMVEERVVSTSDAVDNFMRQIYFESYVRPFVATTRTLGSFTWFPHKTSVPEGEGLHRMGPFSSFVEKVIHKGVERPMFKHDLMMGYAWIDFDIEPARFNQNQLIASGLVDPKFDSLEDFFDAVASLPPGSAKLSQTVRFRVKSQDASFKESFAIHLEYTGSMNQQAKYLVHDVTVMYSGAVSPCVLSDCWRLVLSGPTFKGKSAWYVDTEIINEFLIDTNQLGHVTPVEIVVDMERLQFTEYDFVLVGPCTEPTPLVVHRGGLWECGKKLASFTPVIQDQDLEIFVREVGDTSSDLLIGALSDMMIDRLGLRMQWSGVDIVSTLRAAAPSCEGILSAVLEAVDNWVEFKGYALCYSKSRGKVMVQSSGGKLRLKGRTCEEL MSASKEIKSFLWTQSLRRELSGYCSNIKLQVVKDAQALLHGL MGQIVTFFQEVPHVIEEVMNIVLIALSVLAVLKGLYNFATCGLVGLVTF NucleoproteinDFSEVSNVQRLMRKERRDDNDLKRLRDLNQAVNNLVELKSTQQKSILRVGTLTSDDLLILAADLEKLKSKVIRTERPLSAGVYM Glycoprotein LLLCGRSCTTSLYKGVYELQTLELNMETLNMTMPLSCTKNNSHHYIMVG NETGLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFGNLSSQQLDQRRALLNMIGMSGGNQGARAGRDGVVRVWDVKN NQYEAMSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFMRMAWAELLNNQFGTMPSLTLACLTKQGQVDLNDAVQALTDLGLIYT GGSYIALDSGRGNWDCIMTSYQYLIIQNTTWEDHCQFSRPSPIGYLGLLAKYPNTSDLDRLTQSHPILNMIDTKKSSLNISGYNFSLGAAV SQRTRDIYISRRLLGTFTWTLSDSEGKDTPGGYCLTRWMLIEAELKCFGKAGACMLDGGNMLETIKVSPQTMDGILKSILKVKKALGMFIS NTAVAKCNEKHDEEFCDMLRLFDFNKQAIQRLKAEAQMSIQLINKAVNADTPGERNPYENILYKICLSGDGWPYIASRTSITGRAWENTVV LINDQLIMKNHLRDIMGIPYCNYSKYWYLNHTTTGRTSLPKCWLVSNGSDLESDGKPQKADSNNSSKSLQSAGFTAGLTYSQLMTLKDAMLQLDPNAKTWMDIEGRPEDPVEIALYQPSSGCYIHFFREPTDL YLNETHFSDDIEQQADNMITEMLQKEYMERQGKTPLGLVDLFVFSTSFY LISIFLHLVKIPTHRHIVGKSCPKPHRLNHMGICSCGLYKQPGVPVKWK Nacho CaballeroKQFKQDAKYSHGIDVTDLFATQPGLTSAVIDALPRNMVITCQGSDDIRKLLESQGRKDIKLIDIALSKTDSRKYENAVWDQYKD MGNKQAKAPESKDSPRASLIPDATHLGPQFCKSCWFENKGLVECNNHYL Gracia BonillaLCHMHTGVVVEKKKRGGKEEITPHCALMDCIMFDAAVSGGLNTSVLRAVLPRDMVFRTSTPRVVL Matrix Protein CLNCLTLLLSVSNRCPICKMPLPTKLRPSAAPTAPPTGAADSIRPPPYS AAWTNWDCIMTSYQYLIIQNTTWEDNWDCIMTSYQYLIIQNTTWEDAWE Jaeyoon Chung
    • Lassa feveris currently diagnosed at late stages
    • Interferon Pathway Viralcounteracting strategies Activate Antiviral Response
    • 2-color 3 days postmicroarrays infection Pre Infection
    • We pooled 3 days postsamples by infection timepointbackground corrected andnormalized Pre Infection
    • Log ratios 3 days post infection Sample Log Ratio = Reference Sample Log Ratio = Reference Pre Infection
    • Log Fold 3 days postChange infection Log Fold = Change 3 DPI vs Pre Pre Infection
    • P-value 3 days postdepends on infection number ofindividuals Log Foldvariance of = Change 3 DPI vs Preindividual log ratiosmagnitudeof log fold change Pre Infection
    • 6 DPI 2 vs Pre 8 DPI 3 DPI vs 10 DPI 12 DPI vs Pre vs vs Pre Pre PrePre
    • Probes withsignificant 6 DPIp-values at 2 vs Pre 8 DPI 3 DPI 3 DPI vs 10 DPI 12 DPI vs vs Pre vs vs Pre Pre Pre Pre Pre
    • Probes withsignificant 6 DPIp-values at 2 vs Pre 8 DPI 3 DPI 3 DPI vs 10 DPI 12 DPI vs vs Pre vs vs Pre Pre Pre Pre Pre andsustained log fold changes
    • Immune Cell Types
    • Immune Cell Types
    • Combined vs SubtypesCombined Helper Killer Macrophages B cells white T cells T cellsblood cells
    • CommonResponseLassa Marburg Ebola LCMV Flu
    • UniqueResponse Lassa Marburg Ebola
    • A1BG A2M A2MP1 NAT1 NAT2 AACP SERPINA3 AADAC AAMP AANAT AARS AAVARG1 ARG2 RHOA RHOB RHOC RND3 RHOG ARHGAP1 ARHGAP4 ARHGAP5 ARHGARHGDIA ARHGDIB ARHGDIG RHOH ARL1 PHOX2A ARL2 ARL3 ARNT ARNTL ARRARRB1 ARRB2 ARSA ARSB STS ARSC2 ARSD ARSE ARSF ART1 ART2P ART3 ART4ARVD3 ARVD4 ASAH1 ASCL1 ASCL2 ASD1 ASGR1 ASGR2 ASIP ASL ASLP1 ASMD Most of our candidate genes areASNA1 ASNS ASNSP2 ASPA ASPH ASS1 ASS1P2 ASS1P4 ASS1P5 ASS1P6 ASS1P8ASS1P10 ASS1P14 ASTN1 SERPINC1 ZFHX3 ATD ATF1 ATF3 ATF4 ATF4P1 ATHS A interferon inducedATM RERE ATOH1 ATOX1 ATP1A1 ATP1A2 ATP1A3 ATP12A ATP1A4 ATP1B1 ATPATP1B3 ATP1B3P1 ATP1B1P1 FXYD2 MKKS CHED1 GDF5 MLRG NCOA3 NRIP1 TACHAF1B C21orf33 AABT BAS DGCR6 DVL1L1 LZTR1 IGLJ CLTCL1 DGCR14 OGS2 SGTPBP6 HDHD1 AKAP17A PNPLA4 CND ZRSR2 USP11 USP9X RBM10 KDM5C SMCIDDMX MRXS12 DXS435E MGR2 HNRNPDP BZX GUST INDX NAA10 F8A1 UBL4A Identified an early Lassa-specificTMEM187 LAGE3 SLC10A3 TKTL1 KDM5D USP9Y EPX ARID1A HIST3H3 DYSF COSERF1A HIST1H4I TRRAP PICALM KLRC4 SNN ACOX2 ACOX3 AXIN1 AXIN2 BAP1 pattern of expressionCDC7 CDC45 EOMES FZD1 FZD4 FZD6 FZD7 FZD8 FZD9 GABPAP GFI1B HIST1H2AHIST1H2AK HIST1H2AJ HIST1H2AL HIST1H2APS4 HIST1H2AC HIST1H2AB HISTHIST2H2AA3 HIST2H2AC HIST1H2BG HIST1H2BL HIST1H2BN HIST1H2BM HIST1HIST1H2BE HIST1H2BH HIST1H2BI HIST1H2BC HIST1H2BO HIST2H2BE HIST1H3HIST1H3D HIST1H3C HIST1H3E HIST1H3I HIST1H3G HIST1H3J HIST1H3H HIST1HIST1H4A HIST1H4D HIST1H4F HIST1H4K HIST1H4J HIST1H4C HIST1H4H HIST Carrying out experimentalHIST1H4E HIST1H4L HIST1H4G HIST2H4A HYAL3 IFIT1P1 LOH1CR1 LOH19CR1 M validationNME5 OR1A1 OR1D3P OR1D5 OR1E1 OR1E2 OR1E3 OR1G1 OR1P1 OR3A3 PIP5K1APIP5K1B PIP4K2B PLA2G6 PLA2G10 SCZD6 SCZD7 SLC25A11 SOX14 SPARCL1 SPSRPX TAGLN2 ULK1 UXT RPS9P1 EEA1 BCAR3 ANXA9 STX7 CMAHP BFSP2 SNHGMEHMO BBOX1 LTBP4 ZNF282 STK24 NR0B2 UTF1 RECK SOAT2 SDPR RASAL1 R