Thomas Kepler, PhD

Department:
Biostatistics and Bioinformatics

Email Address:
kepler@duke.edu

Address:
DUMC Box 2721

Durham, NC 27710

Telephone:
9196810620

Research Interests:
Computational and Systems Immunology, Theoretical and Evolutionary Medicine

Publications:
2007 -- Pubmed # 17364079 -- Chan C, Kepler TB. Computational immunology--from bench to virtual reality. Ann Acad Med Singapore. 2007 Feb;36(2):123-7.

2007 -- Pubmed # 17195045 -- Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA, Mohan C, Nachman PH, Clarke SH. Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J Clin Immunol. 2007 Jan;27(1):53-68.

2007 -- Pubmed # 17367341 -- Kepler TB, Chan C. Spatiotemporal programming of a simple inflammatory process. Immunol Rev. 2007 Apr;216:153-63.

2007 -- Pubmed # 17284531 -- Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47.

2007 -- Pubmed # 17967170 -- Ray S, Kepler TB. Amino acid biophysical properties in the statistical prediction of peptide-MHC class I binding. Immunome Res. 2007;3:9.

2006 -- Pubmed # 16733093 -- Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, Heinegård D, Jordan JM, Kepler TB, Lane NE, Saxne T, Tyree B, Kraus VB, . Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage. 2006 Aug;14(8):723-7.

2006 -- Pubmed # 16418189 -- Fadel SA, Cowell LG, Cao S, Ozaki DA, Kepler TB, Steeber DA, Sarzotti M. Neonate-primed CD8+ memory cells rival adult-primed memory cells in antigen-driven expansion and anti-viral protection. Int Immunol. 2006 Feb;18(2):249-57.

2006 -- Pubmed # 16503503 -- Liu C, He M, Rooney B, Kepler TB, Chao NJ. Longitudinal analysis of T-cell receptor variable beta chain repertoire in patients with acute graft-versus-host disease after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2006 Mar;12(3):335-45.

2005 -- Pubmed # 16051675 -- He M, Tomfohr JK, Devlin BH, Sarzotti M, Markert ML, Kepler TB. SpA: web-accessible spectratype analysis: data management, statistical analysis and visualization. Bioinformatics. 2005 Sep 15;21(18):3697-9.

2005 -- Pubmed # 15955781 -- Kepler TB, He M, Tomfohr JK, Devlin BH, Sarzotti M, Markert ML. Statistical analysis of antigen receptor spectratype data. Bioinformatics. 2005 Aug 15;21(16):3394-400.

2005 -- Pubmed # 15987513 -- Lu J, Tomfohr JK, Kepler TB. Identifying differential expression in multiple SAGE libraries: an overdispersed log-linear model approach. BMC Bioinformatics. 2005 Jun 29;6:165.

2005 -- Pubmed # 16156896 -- Tomfohr J, Lu J, Kepler TB. Pathway level analysis of gene expression using singular value decomposition. BMC Bioinformatics. 2005 Sep 12;6:225.

2005 -- Pubmed # 16357034 -- Volpe JM, Cowell LG, Kepler TB. SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations. Bioinformatics. 2005 Dec 15.

2004 -- Pubmed # 14963138 -- Gao F, Chen Y, Levy DN, Conway JA, Kepler TB, Hui H. Unselected mutations in the human immunodeficiency virus type 1 genome are mostly nonsynonymous and often deleterious. J Virol. 2004 Mar;78(5):2426-33.

2004 -- Pubmed # 15199951 -- Loker ES, Adema CM, Zhang SM, Kepler TB. Invertebrate immune systems--not homogeneous, not simple, not well understood. Immunol Rev. 2004 Apr;198:10-24.

2004 -- Pubmed # 15350103 -- Smith JT, Tomfohr JK, Wells MC, Beebe TP Jr, Kepler TB, Reichert WM. Measurement of cell migration on surface-bound fibronectin gradients. Langmuir. 2004 Sep 14;20(19):8279-86.

2004 -- Pubmed # 15247481 -- Zhang SM, Adema CM, Kepler TB, Loker ES. Diversification of Ig superfamily genes in an invertebrate. Science. 2004 Jul 9;305(5681):251-4.

2003 -- Pubmed # 14579105 -- Bartl S, Miracle AL, Rumfelt LL, Kepler TB, Mochon E, Litman GW, Flajnik MF. Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates. Immunogenetics. 2003 Dec;55(9):594-604.

2003 -- Pubmed # 12538660 -- Cowell LG, Davila M, Yang K, Kepler TB, Kelsoe G. Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling. J Exp Med. 2003 Jan 20;197(2):207-20.

2003 -- Pubmed # 12819779 -- Trachtenberg E, Korber B, Sollars C, Kepler TB, Hraber PT, Hayes E, Funkhouser R, Fugate M, Theiler J, Hsu YS, Kunstman K, Wu S, Phair J, Erlich H, Wolinsky S. Advantage of rare HLA supertype in HIV disease progression. Nat Med. 2003 Jul;9(7):928-35.

2002 -- Pubmed # 12537561 -- Cowell LG, Davila M, Kepler TB, Kelsoe G. Identification and utilization of arbitrary correlations in models of recombination signal sequences. Genome Biol. 2002;3(12):RESEARCH0072.

2002 -- Pubmed # 12184811 -- Kepler TB, Crosby L, Morgan KT. Normalization and analysis of DNA microarray data by self-consistency and local regression. Genome Biol. 2002 Jun 28;3(7):RESEARCH0037.

2002 -- Pubmed # 12187936 -- Morgan KT, Ni H, Brown HR, Yoon L, Qualls CW Jr, Crosby LM, Reynolds R, Gaskill B, Anderson SP, Kepler TB, Brainard T, Liv N, Easton M, Merrill C, Creech D, Sprenger D, Conner G, Johnson PR, Fox T, Sartor M, Richard E, Kuruvilla S, Casey W, Benavides G. Application of cDNA microarray technology to in vitro toxicology and the selection of genes for a real-time RT-PCR-based screen for oxidative stress in Hep-G2 cells. Toxicol Pathol. 2002 Jul-Aug;30(4):435-51.

2001 -- Pubmed # 11580104 -- Buchman TG, Cobb JP, Lapedes AS, Kepler TB. Complex systems analysis: a tool for shock research. Shock. 2001 Oct;16(4):248-51.

2001 -- Pubmed # 11720979 -- Kepler TB, Elston TC. Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. Biophys J. 2001 Dec;81(6):3116-36.

2001 -- Pubmed # 11243927 -- Kepler TB, Oprea M. Improved inference of mutation rates: I. An integral representation for the Luria-Delbrück distribution. Theor Popul Biol. 2001 Feb;59(1):41-8.

2001 -- Pubmed # 11145665 -- Oprea M, Cowell LG, Kepler TB. The targeting of somatic hypermutation closely resembles that of meiotic mutation. J Immunol. 2001 Jan 15;166(2):892-9.

2001 -- Pubmed # 11243928 -- Oprea M, Kepler TB. Improved inference of mutation rates: II.Generalization of the Luria-Delbrück distribution for realistic cell-cycle time distributions. Theor Popul Biol. 2001 Feb;59(1):49-59.

2001 -- Pubmed # 11259803 -- Radmacher MD, Kepler TB. Waiting times to appearance and dominance of advantageous mutants: estimation based on the likelihood. Math Biosci. 2001 Mar;170(1):59-77.

2001 -- Pubmed # 11682302 -- Zavolan M, Kepler TB. Statistical inference of sequence-dependent mutation rates. Curr Opin Genet Dev. 2001 Dec;11(6):612-5.

2000 -- Pubmed # 10657647 -- Cowell LG, Kepler TB. The nucleotide-replacement spectrum under somatic hypermutation exhibits microsequence dependence that is strand-symmetric and distinct from that under germline mutation. J Immunol. 2000 Feb 15;164(4):1971-6.

2000 -- Pubmed # 11133343 -- Crosby LM, Hyder KS, DeAngelo AB, Kepler TB, Gaskill B, Benavides GR, Yoon L, Morgan KT. Morphologic analysis correlates with gene expression changes in cultured F344 rat mesothelial cells. Toxicol Appl Pharmacol. 2000 Dec 15;169(3):205-21.

2000 -- Pubmed # 10696765 -- Keys DA, Wallace DG, Kepler TB, Conolly RB. Quantitative evaluation of alternative mechanisms of blood disposition of di(n-butyl) phthalate and mono(n-butyl) phthalate in rats. Toxicol Sci. 2000 Feb;53(2):173-84.

1999 -- Pubmed # 10480635 -- Betts MR, Krowka JF, Kepler TB, Davidian M, Christopherson C, Kwok S, Louie L, Eron J, Sheppard H, Frelinger JA. Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1-infected long-term survivors. AIDS Res Hum Retroviruses. 1999 Sep 1;15(13):1219-28.

1999 -- Pubmed # 10368430 -- Cowell LG, Kim HJ, Humaljoki T, Berek C, Kepler TB. Enhanced evolvability in immunoglobulin V genes under somatic hypermutation. J Mol Evol. 1999 Jul;49(1):23-6.

1999 -- Pubmed # 10079104 -- Gangi-Peterson L, Sorscher DH, Reynolds JW, Kepler TB, Mitchell BS. Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination. J Clin Invest. 1999 Mar;103(6):833-41.

1999 -- Pubmed # 10416263 -- Keys DA, Wallace DG, Kepler TB, Conolly RB. Quantitative evaluation of alternative mechanisms of blood and testes disposition of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in rats. Toxicol Sci. 1999 Jun;49(2):172-85.

1999 -- Pubmed # 10613852 -- Oprea M, Kepler TB. Genetic plasticity of V genes under somatic hypermutation: statistical analyses using a new resampling-based methodology. Genome Res. 1999 Dec;9(12):1294-304.

1998 -- Pubmed # 9473394 -- Cowell LG, Crowder LB, Kepler TB. Density-dependent prenatal androgen exposure as an endogenous mechanism for the generation of cycles in small mammal populations J Theor Biol. 1998 Jan 7;190(1):93-106.

1998 -- Pubmed # 9477340 -- Cowell LG, Kepler TB, Janitz M, Lauster R, Mitchison NA. The distribution of variation in regulatory gene segments, as present in MHC class II promoters. Genome Res. 1998 Feb;8(2):124-34.

1998 -- Pubmed # 9479853 -- Kepler TB, Bartl S. Plasticity under somatic mutation in antigen receptors. Curr Top Microbiol Immunol. 1998;229:149-62.

1998 -- Pubmed # 9751697 -- Kepler TB, Perelson AS. Drug concentration heterogeneity facilitates the evolution of drug resistance. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11514-9.

1998 -- Pubmed # 9723780 -- Radmacher MD, Kelsoe G, Kepler TB. Predicted and inferred waiting times for key mutations in the germinal centre reaction: evidence for stochasticity in selection. Immunol Cell Biol. 1998 Aug;76(4):373-81.

1997 -- Pubmed # 9190065 -- Kepler TB. Codon bias and plasticity in immunoglobulins. Mol Biol Evol. 1997 Jun;14(6):637-43.

1996 -- Pubmed # 8906821 -- Kepler TB, Borrero M, Rugerio B, McCray SK, Clarke SH. Interdependence of N nucleotide addition and recombination site choice in V(D)J rearrangement. J Immunol. 1996 Nov 15;157(10):4451-7.

1995 -- Pubmed # 7541819 -- Han S, Hathcock K, Zheng B, Kepler TB, Hodes R, Kelsoe G. Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. J Immunol. 1995 Jul 15;155(2):556-67.

1995 -- Pubmed # 7667271 -- Kepler TB, Perelson AS. Modeling and optimization of populations subject to time-dependent mutation. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8219-23.

1993 -- Pubmed # 8452888 -- Kepler TB, Marder E. Spike initiation and propagation on axons with slow inward currents. Biol Cybern. 1993;68(3):209-14.

1993 -- Pubmed # 8397781 -- Kepler TB, Perelson AS. Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation. Immunol Today. 1993 Aug;14(8):412-5.

1993 -- Pubmed # 8264243 -- Kepler TB, Perelson AS. Somatic hypermutation in B cells: an optimal control treatment. J Theor Biol. 1993 Sep 7;164(1):37-64.

1992 -- Pubmed # 1562643 -- Kepler TB, Abbott LF, Marder E. Reduction of conductance-based neuron models. Biol Cybern. 1992;66(5):381-7.

1991 -- Pubmed # 1992353 -- Kagan ML, Kepler TB, Epstein IR. Geometric phase shifts in chemical oscillators. Nature. 1991 Feb 7;349(6309):506-8.

1991 -- Pubmed # 12779941 -- Kepler TB, Kagan ML, Epstein IR. Geometric phases in dissipative systems. Chaos. 1991 Dec;1(4):455-461.

1991 -- Pubmed # 10043921 -- Kepler TB, Kagan ML. Geometric phase shifts under adiabatic parameter changes in classical dissipative systems. PHYSICAL REVIEW LETTERS. 1991 Feb 18;66(7):847-849.

1990 -- Pubmed # 2321028 -- Kepler TB, Marder E, Abbott LF. The effect of electrical coupling on the frequency of model neuronal oscillators. Science. 1990 Apr 6;248(4951):83-5.