Thomas B Kepler, Professor of Biostatistics and Bioinformatics and Chief, Computational Biology

Office Location:  101A North Building
Office Phone:  (919) 681-0620
Email Address: send me a message
Web Page:  http://faculty.duhs.duke.edu/faculty/info?pid=6764

Education:

Ph.D.Brandeis University1989
B.A.University Of Massachusetts At Amherst1985
Research Interests:

Computational and Systems Immunology, Theoretical and Evolutionary Medicine

Keywords:

Mutation • Data Interpretation, Statistical • Models, Genetic • Statistical Distributions • Statistics • Models, Biological • Drug Resistance, Microbial • Evolution • Codon • Variation (Genetics) • Selection (Genetics) • Genes, MHC Class II • Models, Neurological • Neural Conduction • Germinal Center • Models, Chemical • Gene Expression Regulation • Stochastic Processes • Transcription, Genetic • Genome • Recombination, Genetic • HIV Long-Term Survivors • Genes, Immunoglobulin • Antigens, CD • Algorithms • Models, Immunological • Database Management Systems • Databases, Protein • Immune System • Allergy and Immunology • Computational Biology • Immunity, Natural • Autoimmune Diseases • Rheumatology

Representative Publications

  1. ML Markert, BH Devlin, MJ Alexieff, J Li, EA McCarthy, SE Gupton, IK Chinn, LP Hale, TB Kepler, M He, M Sarzotti, MA Skinner, HE Rice, JC Hoehner, Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants., Blood, United States, vol. 109 no. 10 (May, 2007), pp. 4539-47, ISSN 0006-4971  [abs]
  2. TB Kepler, C Chan, Spatiotemporal programming of a simple inflammatory process., Immunological reviews, Denmark, vol. 216 (April, 2007), pp. 153-63, ISSN 0105-2896  [abs]
  3. C Chan, TB Kepler, Computational immunology--from bench to virtual reality., Annals of the Academy of Medicine, Singapore, Singapore, vol. 36 no. 2 (February, 2007), pp. 123-7, ISSN 0304-4602  [abs]
  4. DA Culton, MW Nicholas, DO Bunch, QL Zhen, TB Kepler, MA Dooley, C Mohan, PH Nachman, SH Clarke, Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss., Journal of clinical immunology, United States, vol. 27 no. 1 (January, 2007), pp. 53-68, ISSN 0271-9142  [abs]
  5. S Ray, TB Kepler, Amino acid biophysical properties in the statistical prediction of peptide-MHC class I binding., Immunome research, England, vol. 3 (2007), pp. 9, ISSN 1745-7580  [abs]
  6. DC Bauer, DJ Hunter, SB Abramson, M Attur, M Corr, D Felson, D Heinegård, JM Jordan, TB Kepler, NE Lane, T Saxne, B Tyree, VB Kraus, Osteoarthritis Biomarkers Network, Classification of osteoarthritis biomarkers: a proposed approach., Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, England, vol. 14 no. 8 (August, 2006), pp. 723-7, ISSN 1063-4584  [abs]
  7. C Liu, M He, B Rooney, TB Kepler, NJ Chao, Longitudinal analysis of T-cell receptor variable beta chain repertoire in patients with acute graft-versus-host disease after allogeneic stem cell transplantation., Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, United States, vol. 12 no. 3 (March, 2006), pp. 335-45, ISSN 1083-8791  [abs]
  8. SA Fadel, LG Cowell, S Cao, DA Ozaki, TB Kepler, DA Steeber, M Sarzotti, Neonate-primed CD8+ memory cells rival adult-primed memory cells in antigen-driven expansion and anti-viral protection., International immunology, England, vol. 18 no. 2 (February, 2006), pp. 249-57, ISSN 0953-8178  [abs]
  9. JM Volpe, LG Cowell, TB Kepler, SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations., Bioinformatics (Oxford, England), England, vol. 22 no. 4 (February, 2006), pp. 438-44, ISSN 1367-4803  [abs]
  10. M He, JK Tomfohr, BH Devlin, M Sarzotti, ML Markert, TB Kepler, SpA: web-accessible spectratype analysis: data management, statistical analysis and visualization., Bioinformatics (Oxford, England), England, vol. 21 no. 18 (September, 2005), pp. 3697-9, ISSN 1367-4803  [abs]
  11. TB Kepler, M He, JK Tomfohr, BH Devlin, M Sarzotti, ML Markert, Statistical analysis of antigen receptor spectratype data., Bioinformatics (Oxford, England), England, vol. 21 no. 16 (August, 2005), pp. 3394-400, ISSN 1367-4803  [abs]
  12. J Lu, JK Tomfohr, TB Kepler, Identifying differential expression in multiple SAGE libraries: an overdispersed log-linear model approach., BMC bioinformatics, England, vol. 6 (2005), pp. 165, ISSN 1471-2105  [abs]
  13. J Tomfohr, J Lu, TB Kepler, Pathway level analysis of gene expression using singular value decomposition., BMC bioinformatics, England, vol. 6 (2005), pp. 225, ISSN 1471-2105  [abs]
  14. JT Smith, JK Tomfohr, MC Wells, TP Beebe, TB Kepler, WM Reichert, Measurement of cell migration on surface-bound fibronectin gradients., Langmuir : the ACS journal of surfaces and colloids, United States, vol. 20 no. 19 (September, 2004), pp. 8279-86, ISSN 0743-7463  [abs]
  15. SM Zhang, CM Adema, TB Kepler, ES Loker, Diversification of Ig superfamily genes in an invertebrate., Science (New York, N.Y.), United States, vol. 305 no. 5681 (July, 2004), pp. 251-4, ISSN 1095-9203  [abs]
  16. ES Loker, CM Adema, SM Zhang, TB Kepler, Invertebrate immune systems--not homogeneous, not simple, not well understood., Immunological reviews, Denmark, vol. 198 (April, 2004), pp. 10-24, ISSN 0105-2896  [abs]
  17. F Gao, Y Chen, DN Levy, JA Conway, TB Kepler, H Hui, Unselected mutations in the human immunodeficiency virus type 1 genome are mostly nonsynonymous and often deleterious., Journal of virology, United States, vol. 78 no. 5 (March, 2004), pp. 2426-33, ISSN 0022-538X  [abs]
  18. S Bartl, AL Miracle, LL Rumfelt, TB Kepler, E Mochon, GW Litman, MF Flajnik, Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural conservation within vertebrates., Immunogenetics, United States, vol. 55 no. 9 (December, 2003), pp. 594-604, ISSN 0093-7711  [abs]
  19. E Trachtenberg, B Korber, C Sollars, TB Kepler, PT Hraber, E Hayes, R Funkhouser, M Fugate, J Theiler, YS Hsu, K Kunstman, S Wu, J Phair, H Erlich, S Wolinsky, Advantage of rare HLA supertype in HIV disease progression., Nature medicine, United States, vol. 9 no. 7 (July, 2003), pp. 928-35, ISSN 1078-8956  [abs]
  20. LG Cowell, M Davila, K Yang, TB Kepler, G Kelsoe, Prospective estimation of recombination signal efficiency and identification of functional cryptic signals in the genome by statistical modeling., The Journal of experimental medicine, United States, vol. 197 no. 2 (January, 2003), pp. 207-20, ISSN 0022-1007  [abs]
  21. TB Kepler, L Crosby, KT Morgan, Normalization and analysis of DNA microarray data by self-consistency and local regression., Genome biology, England, vol. 3 no. 7 (June, 2002), pp. RESEARCH0037, ISSN 1465-6914  [abs]
  22. LG Cowell, M Davila, TB Kepler, G Kelsoe, Identification and utilization of arbitrary correlations in models of recombination signal sequences., Genome biology, England, vol. 3 no. 12 (2002), pp. RESEARCH0072, ISSN 1465-6914  [abs]
  23. M Zavolan, TB Kepler, Statistical inference of sequence-dependent mutation rates., Current opinion in genetics & development, England, vol. 11 no. 6 (December, 2001), pp. 612-5, ISSN 0959-437X  [abs]
  24. TB Kepler, TC Elston, Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations., Biophysical journal, United States, vol. 81 no. 6 (December, 2001), pp. 3116-36, ISSN 0006-3495  [abs]
  25. TG Buchman, JP Cobb, AS Lapedes, TB Kepler, Complex systems analysis: a tool for shock research., Shock (Augusta, Ga.), United States, vol. 16 no. 4 (October, 2001), pp. 248-51, ISSN 1073-2322  [abs]
  26. MD Radmacher, TB Kepler, Waiting times to appearance and dominance of advantageous mutants: estimation based on the likelihood., Mathematical biosciences, United States, vol. 170 no. 1 (March, 2001), pp. 59-77, ISSN 0025-5564  [abs]
  27. TB Kepler, M Oprea, Improved inference of mutation rates: I. An integral representation for the Luria-Delbrück distribution., Theoretical population biology, United States, vol. 59 no. 1 (February, 2001), pp. 41-8, ISSN 0040-5809  [abs]
  28. M Oprea, TB Kepler, Improved inference of mutation rates: II.Generalization of the Luria-Delbrück distribution for realistic cell-cycle time distributions., Theoretical population biology, United States, vol. 59 no. 1 (February, 2001), pp. 49-59, ISSN 0040-5809  [abs]
  29. M Oprea, LG Cowell, TB Kepler, The targeting of somatic hypermutation closely resembles that of meiotic mutation., Journal of immunology (Baltimore, Md. : 1950), UNITED STATES, vol. 166 no. 2 (January, 2001), pp. 892-9, ISSN 0022-1767  [abs]
  30. LM Crosby, KS Hyder, AB DeAngelo, TB Kepler, B Gaskill, GR Benavides, L Yoon, KT Morgan, Morphologic analysis correlates with gene expression changes in cultured F344 rat mesothelial cells., Toxicology and applied pharmacology, UNITED STATES, vol. 169 no. 3 (December, 2000), pp. 205-21, ISSN 0041-008X  [abs]
  31. DA Keys, DG Wallace, TB Kepler, RB Conolly, Quantitative evaluation of alternative mechanisms of blood disposition of di(n-butyl) phthalate and mono(n-butyl) phthalate in rats., Toxicological sciences : an official journal of the Society of Toxicology, UNITED STATES, vol. 53 no. 2 (February, 2000), pp. 173-84, ISSN 1096-6080  [abs]
  32. LG Cowell, TB Kepler, The nucleotide-replacement spectrum under somatic hypermutation exhibits microsequence dependence that is strand-symmetric and distinct from that under germline mutation., Journal of immunology (Baltimore, Md. : 1950), UNITED STATES, vol. 164 no. 4 (February, 2000), pp. 1971-6, ISSN 0022-1767  [abs]
  33. M Oprea, TB Kepler, Genetic plasticity of V genes under somatic hypermutation: statistical analyses using a new resampling-based methodology., Genome research, UNITED STATES, vol. 9 no. 12 (December, 1999), pp. 1294-304, ISSN 1088-9051  [abs]
  34. MR Betts, JF Krowka, TB Kepler, M Davidian, C Christopherson, S Kwok, L Louie, J Eron, H Sheppard, JA Frelinger, 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 research and human retroviruses, UNITED STATES, vol. 15 no. 13 (September, 1999), pp. 1219-28, ISSN 0889-2229  [abs]
  35. LG Cowell, HJ Kim, T Humaljoki, C Berek, TB Kepler, Enhanced evolvability in immunoglobulin V genes under somatic hypermutation., Journal of molecular evolution, UNITED STATES, vol. 49 no. 1 (July, 1999), pp. 23-6, ISSN 0022-2844  [abs]
  36. DA Keys, DG Wallace, TB Kepler, RB Conolly, Quantitative evaluation of alternative mechanisms of blood and testes disposition of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in rats., Toxicological sciences : an official journal of the Society of Toxicology, UNITED STATES, vol. 49 no. 2 (June, 1999), pp. 172-85, ISSN 1096-6080  [abs]
  37. L Gangi-Peterson, DH Sorscher, JW Reynolds, TB Kepler, BS Mitchell, Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination., The Journal of clinical investigation, UNITED STATES, vol. 103 no. 6 (March, 1999), pp. 833-41, ISSN 0021-9738  [abs]
  38. TB Kepler, AS Perelson, Drug concentration heterogeneity facilitates the evolution of drug resistance., Proceedings of the National Academy of Sciences of the United States of America, UNITED STATES, vol. 95 no. 20 (September, 1998), pp. 11514-9, ISSN 0027-8424  [abs]
  39. MD Radmacher, G Kelsoe, TB Kepler, Predicted and inferred waiting times for key mutations in the germinal centre reaction: evidence for stochasticity in selection., Immunology and cell biology, AUSTRALIA, vol. 76 no. 4 (August, 1998), pp. 373-81, ISSN 0818-9641  [abs]
  40. LG Cowell, TB Kepler, M Janitz, R Lauster, NA Mitchison, The distribution of variation in regulatory gene segments, as present in MHC class II promoters., Genome research, UNITED STATES, vol. 8 no. 2 (February, 1998), pp. 124-34, ISSN 1088-9051  [abs]
  41. LG Cowell, LB Crowder, TB Kepler, Density-dependent prenatal androgen exposure as an endogenous mechanism for the generation of cycles in small mammal populations , J Theor Biol, vol. 190 no. 1 (January, 1998), pp. 93-106, ISSN 0022-5193  [abs]
  42. TB Kepler, S Bartl, Plasticity under somatic mutation in antigen receptors., Current topics in microbiology and immunology, GERMANY, vol. 229 (1998), pp. 149-62, ISSN 0070-217X
  43. TB Kepler, Codon bias and plasticity in immunoglobulins., Molecular biology and evolution, UNITED STATES, vol. 14 no. 6 (June, 1997), pp. 637-43, ISSN 0737-4038  [abs]
  44. TB Kepler, M Borrero, B Rugerio, SK McCray, SH Clarke, Interdependence of N nucleotide addition and recombination site choice in V(D)J rearrangement., Journal of immunology (Baltimore, Md. : 1950), UNITED STATES, vol. 157 no. 10 (November, 1996), pp. 4451-7, ISSN 0022-1767  [abs]
  45. TB Kepler, AS Perelson, Modeling and optimization of populations subject to time-dependent mutation., Proceedings of the National Academy of Sciences of the United States of America, UNITED STATES, vol. 92 no. 18 (August, 1995), pp. 8219-23, ISSN 0027-8424  [abs]
  46. S Han, K Hathcock, B Zheng, TB Kepler, R Hodes, G Kelsoe, Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers., Journal of immunology (Baltimore, Md. : 1950), UNITED STATES, vol. 155 no. 2 (July, 1995), pp. 556-67, ISSN 0022-1767  [abs]
  47. TB Kepler, AS Perelson, Somatic hypermutation in B cells: an optimal control treatment., Journal of theoretical biology, ENGLAND, vol. 164 no. 1 (September, 1993), pp. 37-64, ISSN 0022-5193  [abs]
  48. TB Kepler, AS Perelson, Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation., Immunology today, ENGLAND, vol. 14 no. 8 (August, 1993), pp. 412-5, ISSN 0167-5699  [abs]
  49. TB Kepler, E Marder, Spike initiation and propagation on axons with slow inward currents., Biological cybernetics, GERMANY, vol. 68 no. 3 (1993), pp. 209-14, ISSN 0340-1200  [abs]
  50. TB Kepler, LF Abbott, E Marder, Reduction of conductance-based neuron models., Biological cybernetics, GERMANY, vol. 66 no. 5 (1992), pp. 381-7, ISSN 0340-1200  [abs]
  51. TB Kepler, ML Kagan, IR Epstein, Geometric phases in dissipative systems., Chaos, vol. 1 no. 4 (December, 1991), pp. 455-461, ISSN 1054-1500  [abs]
  52. ML Kagan, TB Kepler, IR Epstein, Geometric phase shifts in chemical oscillators., Nature, ENGLAND, vol. 349 no. 6309 (February, 1991), pp. 506-8, ISSN 0028-0836  [abs]
  53. TB Kepler, ML Kagan, Geometric phase shifts under adiabatic parameter changes in classical dissipative systems., Phys Rev Lett, vol. 66 no. 7 (February, 1991), pp. 847-849, ISSN 0031-9007
  54. TB Kepler, E Marder, LF Abbott, The effect of electrical coupling on the frequency of model neuronal oscillators., Science (New York, N.Y.), UNITED STATES, vol. 248 no. 4951 (April, 1990), pp. 83-5, ISSN 0036-8075  [abs]
  55. KT Morgan, H Ni, HR Brown, L Yoon, CW Qualls, LM Crosby, R Reynolds, B Gaskill, SP Anderson, TB Kepler, T Brainard, N Liv, M Easton, C Merrill, D Creech, D Sprenger, G Conner, PR Johnson, T Fox, M Sartor, E Richard, S Kuruvilla, W Casey, G Benavides, 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., Toxicologic pathology, United States, vol. 30 no. 4 , pp. 435-51, ISSN 0192-6233  [abs]