Date: Mon, 22 Sep 2008 22:02:04 -0400 From: Alfred Hero To: Christopher W Woods CC: Tim Veldman , Aimee Zaas , "Alfred O. Hero" , Brett Caram , Carolyn Talcott , Christine Oien , Geoffrey Ginsburg , Jay B Varkey , Lawrence Carin , Patrick Lincoln , Rita L Chambers , Sara Hoffman , Stephen Kingsmore , "'Eley, Greg [USA]'" Subject: FIndings for RSV RBM samples Team - here are some early results on the RSV proteomic samples processed by Rules Based Medicine that I can briefly discuss tomorrow at the telecon. Comments: a. Several of the 90 proteomic marker levels were too saturated (either too low or too high) to be measured accurately. b. Regularized log transformation was applied to proteomic data prior to analysis. c. altogether the proteomics are not nearly as significant as mRNA in terms of differential expression d: this represents differential expression analysis only. Prediction analysis will be ready in a couple of days. Findings: A. Screening for persistent biomarkers over 0.1T, 0.2T, 0.8T: We screened the merged list of mRNA and proteomic biomarkers for differential expression btwn sx and asx (using multiple comparison Behrens-Fisher unpaired t-test of significance): Finding 1: if one only had access to proteomic biomarkers there are only 4 of 90 that come up as significantly differentially expressed (q=0.2) 'Myeloperoxidase' 'MMP-2' 'Myoglobin' 'IgE ' Finding 2: proteomic biomarkers are not competitive with mRNA. Out of the merged proteomic+mRNA list only 5 are significant at q=0.2. 'CD177', 'TXNDC3', 'CD72', 'UPK2', 'CD22 First proteomic entry on merged p-value list has rank #21: rank 1 rank 2 rank 3 rank 4 rank 5 .... rank 21 'CD177', 'TXNDC3', 'CD72', 'UPK2', 'CD22...''Myeloperoxidase'' The p-value of Myeloperoxidase is order of magnitude better (0.0004) than others on proteomic list. This pvalue is itself an order of magnitude worse than that of the top ranked mRNA biomarker CD177 (pv=6 10-7). Finding 3: Attached are time courses of these biomarkers over (A,S)=(asx, sx) across all 6 time points (BL, 0, 0.1, 0.2, 0.8, 1). Time course of CD177 shows good separation of sx and asx even at prechallenge and BL. Note also the much higher spread of IgE levels in asx than in sx at all 6 sample times - a fluke? B. Screening over 0.1T, 0.2T, 0.8T, T: The significant (q=0.2) merged biomarkers are the following 215 genes plus Myeloperoxidase : 'CD177' 'TXNDC3' 'CD72' 'CD22' 'TUBB2A' 'ID3' 'FCER2' 'IGHM' 'FZD2' 'SPOP' 'P2RX5' 'H1F0' 'CD79B' 'SERTAD2' 'IA_Myeloperoxidase' 'C11orf49' 'PASK' 'VPREB3' 'CD79A' 'TSPAN3' 'PANK2' 'IGHD' 'DTX4' 'NGDN' 'ZNF266' 'MICAL3' 'CD19' 'SP140' 'GPR18' 'SETD6' 'RNF125' 'HHEX' 'LRRC14' 'PPT1' 'BST2' 'IGHV1-69' 'CUBN' 'CRTAM' 'TXNDC13' 'CR2' 'FLVCR2' 'NIT1' 'FCRL2' 'KCNMB1' 'TRAV13-2' 'BLNK' 'SHMT2' 'DNAL4' 'AP3S2' 'RPUSD2' 'TCL1A' 'C5orf4' 'KIAA0125' 'ABT1' 'GLB1L' 'OSBPL10' 'HLA-DQA1' 'ETV7' 'BLK' 'PHF11' 'FIG4' 'NMT2' 'ZMAT3' 'MMP10' 'GJA5' 'HMBOX1' 'ATP2C2' 'CNPY2' 'RUVBL1' 'TRAV21' 'IA_MMP-2' 'MS4A1' 'SPIN1' 'CPSF3L' 'BACH2' 'PCSK6' 'CHD1L' 'SLC31A1' 'IPP' 'FCN2' 'C11orf80' 'HLA-DOB' 'C3orf37' 'TLR7' 'P2RY6' 'SPIB' 'CCBP2' 'TRAV36DV7' 'ZNF133' 'SWAP70' 'LIMA1' 'SYPL1' 'CORO2B' 'MRPL48' 'SLC4A7' 'RBBP7' 'PTPRK' 'IA_IgE ' 'CXorf1' 'CASP10' 'ARHGAP6' 'CACYBP' 'MAK10' 'SRGAP2' 'TRAC' 'ADARB1' 'TRAV9-2' 'PVRL2' 'PTPN7' 'C17orf48' 'UFM1' 'TUBB6' 'TMEM180' 'CCR6' 'ZNF639' 'ITFG2' 'PWP1' 'HLA-B' 'CD6' 'ERP29' 'RRM1' 'ZBP1' 'C21orf59' 'C10orf38' 'SRPRB' 'TCF4' 'EIF3I' 'TSPYL4' 'CNDP2' 'FXC1' 'BCL11A' 'FOXO1' 'IL32' 'GP1BA' 'QTRT1' 'POLR1C' 'GGA1' 'CBS' 'TIMM44' 'GSPT2' 'ZNF419' 'MGC3196' 'CRIP1' 'TOX4' 'AP1G1' 'PDCD4' 'IL18RAP' 'PDE4DIP' 'NFX1' 'CLEC1B' 'SLC35E2' 'GPHN' 'SIRPG' 'RMND1' 'TRAF6' 'SEMA6A' 'SLAMF1' 'ASTE1' 'ESD' 'P2RY10' 'GLS' 'ALMS1' 'PCYOX1' 'PRKCE' 'BANK1' 'IKBKAP' 'CPNE3' 'DNAJC16' 'LCP1' 'DYRK2' 'MLLT11' 'ADSL' 'ISG20L2' 'HMOX1' 'PRMT1' 'TICAM1' 'MX1' 'TM9SF1' 'ARHGAP12' 'KIAA0746' 'RSL1D1' 'SCLY' 'FDFT1' 'P2RX1' 'C12orf41' 'IFIT2' 'RFC4' 'ADAM28' 'HERC6' 'METTL8' 'C13orf18' 'TTC12' 'ANKRD46' 'CEBPG' 'PNOC' 'NPY5R' 'LOC130074' 'MINA' 'TRIM38' 'TLR5' 'PKIG' 'CARS2' '2-Sep' 'IFIT3' 'LRFN3' 'TSEN2' 'CIDEC' 'PPARD' 'HLA-DQB1' 'HHLA3' 'GCC2' 'FAHD2A' 'MPL' 'PRKRIR' 'C1orf107' 'DOCK5' . Christopher W Woods wrote: > > I will be returning from europe. Not sure I will make it. > > ------------------------------------------------------------------------ > > * From: *"Tim Veldman" [Tim.Veldman@duke.edu] > * Sent: *09/22/2008 04:30 PM AST > * To: *Aimee Zaas; "Alfred O. Hero" ; "Brett > Caram" ; "Carolyn Talcott" ; > Christine Oien; Christopher Woods; Geoffrey Ginsburg; Jay Varkey; > "Lawrence Carin" ; "Patrick Lincoln" > ; Rita Chambers; "Sara Hoffman" > ; "Stephen Kingsmore" > * Cc: *"'Eley, Greg [USA]'" > * Subject: *REminder: PHD Project Team Meeting 9/23 1130AM EDT > > > Hi All, > > > > This is a reminder that the PHD team meeting is tomorrow at 1130AM > EDT. Please note, given the short agenda, I suspect we will not > require the full hour. > > > > Dial-in number 1-877-860-3058 > > Passcode 165432# > > > > Agenda topics: > > > > 1. Updates on the data analysis from the RSV study > 2. Regulatory updates –IRB submissions and approval timelines – IRB > comments from SRI and Duke > 3. Other business > > > > Many thanks. > > > > ------------------------------------- > > Tim H. Veldman, PhD > > Genomic Medicine Program Manager > > Institute for Genome Sciences and Policy > > Duke University Medical Center > > 127C North Bldg, Box 90141 > > 470 Research Drive > > Durham, NC 27708 > > 919-684-5479 (O) > > 919-668-2465 (F) > > 919-418-0037 (M) > > > -- ----------------- Alfred Hero University of Michigan Ann Arbor, MI 48109-2122 Tel: 734 763 0564 Fax: 734 763 8041 www.eecs.umich.edu/~hero