Keywords
Last Name

Thomas Kepler, PhD

TitleProfessor
InstitutionBoston University School of Medicine
DepartmentMicrobiology
Address80 E. Concord St Housman (R)
Boston MA 02118
Phone(617) 638-4124
ORCID ORCID Icon0000-0002-1383-6865
Other Positions
TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine
DepartmentGraduate Medical Sciences, Division of

TitleMember
InstitutionBoston University
DepartmentBioinformatics Graduate Program

 Research Expertise & Professional Interests
The Kepler laboratory develops computational tools and applies them in the context of systems-level experimentation to address outstanding questions in immunology and vaccine development. Much of their work is centered on antibodies and the cells (B cells) that produce them.

Antibodies are genetically extraordinary: their genes are encoded only as fragments in the genome. The B cell’s genome must be cut, rearranged and re-ligated in several places to make the genes required for antibody production. Furthermore, after a B cell has encountered a molecule that binds its antibody (whether on a pathogen, an infected cell, a cancerous tumor, or, in the case of autoimmune disease, normal tissue) the B cell directs mutations into its rearranged antibody genes, and is then subject to competitive selection for improved ability to bind the eliciting molecule. In this Darwinian process, known as affinity maturation, the antibody response is rapidly improved and prepared as the memory response that confers long-term immunity and serves as the basis for vaccination.

The Kepler group works with multiple collaborating laboratories to generate and integrate data from many different assays, each of which provides one perspective on the workings of affinity maturation. By using computational means to coordinate the integration of these diverse data, a comprehensive picture of the process at a systems level emerges.

Professor Kepler, in partnership with colleagues at Duke and Harvard Universities, has developed a new approach to vaccination that uses computational methods to select combinations of immunogens to use in vaccines that drive affinity maturation in specific directions. These methods are being used to develop vaccines against HIV, influenza, and anthrax.

 Self-Described Keywords
  • affinity maturation
  • antibody
  • B cell
  • bats
  • computational biology
  • mathematical modeling
  • systems biology
  • vaccine
  • wildlife immunology
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Nair SK, Tomaras GD, Sales AP, Boczkowski D, Chan C, Plonk K, Cai Y, Dannull J, Kepler TB, Pruitt SK, Weinhold KJ. High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes. Sci Rep. 2014; 4:4632.
    View in: PubMed
  2. Kepler TB, Munshaw S, Wiehe K, Zhang R, Yu JS, Woods CW, Denny TN, Tomaras GD, Alam SM, Moody MA, Kelsoe G, Liao HX, Haynes BF. Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation. Front Immunol. 2014; 5:170.
    View in: PubMed
  3. Bonsignori M, Wiehe K, Grimm SK, Lynch R, Yang G, Kozink DM, Perrin F, Cooper AJ, Hwang KK, Chen X, Liu M, McKee K, Parks RJ, Eudailey J, Wang M, Clowse M, Criscione-Schreiber LG, Moody MA, Ackerman ME, Boyd SD, Gao F, Kelsoe G, Verkoczy L, Tomaras GD, Liao HX, Kepler TB, Montefiori DC, Mascola JR, Haynes BF. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. J Clin Invest. 2014 Apr 1; 124(4):1835-43.
    View in: PubMed
  4. Lynch HE, Stewart SM, Kepler TB, Sempowski GD, Alam SM. Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen. J Immunol Methods. 2014 Feb; 404:1-12.
    View in: PubMed
  5. Alam SM, Dennison SM, Aussedat B, Vohra Y, Park PK, Fernández-Tejada A, Stewart S, Jaeger FH, Anasti K, Blinn JH, Kepler TB, Bonsignori M, Liao HX, Sodroski JG, Danishefsky SJ, Haynes BF. Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors. Proc Natl Acad Sci U S A. 2013 Nov 5; 110(45):18214-9.
    View in: PubMed
  6. Wesemann DR, Portuguese AJ, Meyers RM, Gallagher MP, Cluff-Jones K, Magee JM, Panchakshari RA, Rodig SJ, Kepler TB, Alt FW. Microbial colonization influences early B-lineage development in the gut lamina propria. Nature. 2013 Sep 5; 501(7465):112-5.
    View in: PubMed
  7. Ciupe SM, Devlin BH, Markert ML, Kepler TB. Quantification of total T-cell receptor diversity by flow cytometry and spectratyping. BMC Immunol. 2013; 14:35.
    View in: PubMed
  8. Kepler TB. Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors. F1000Res. 2013; 2:103.
    View in: PubMed
  9. Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 25; 496(7446):469-76.
    View in: PubMed
  10. Yang G, Holl TM, Liu Y, Li Y, Lu X, Nicely NI, Kepler TB, Alam SM, Liao HX, Cain DW, Spicer L, VandeBerg JL, Haynes BF, Kelsoe G. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J Exp Med. 2013 Feb 11; 210(2):241-56.
    View in: PubMed
  11. Liao HX, Bonsignori M, Alam SM, McLellan JS, Tomaras GD, Moody MA, Kozink DM, Hwang KK, Chen X, Tsao CY, Liu P, Lu X, Parks RJ, Montefiori DC, Ferrari G, Pollara J, Rao M, Peachman KK, Santra S, Letvin NL, Karasavvas N, Yang ZY, Dai K, Pancera M, Gorman J, Wiehe K, Nicely NI, Rerks-Ngarm S, Nitayaphan S, Kaewkungwal J, Pitisuttithum P, Tartaglia J, Sinangil F, Kim JH, Michael NL, Kepler TB, Kwong PD, Mascola JR, Nabel GJ, Pinter A, Zolla-Pazner S, Haynes BF. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity. 2013 Jan 24; 38(1):176-86.
    View in: PubMed
  12. Chan C, Billard M, Ramirez SA, Schmidl H, Monson E, Kepler TB. A model for migratory B cell oscillations from receptor down-regulation induced by external chemokine fields. Bull Math Biol. 2013 Jan; 75(1):185-205.
    View in: PubMed
  13. Schmidt AG, Xu H, Khan AR, O'Donnell T, Khurana S, King LR, Manischewitz J, Golding H, Suphaphiphat P, Carfi A, Settembre EC, Dormitzer PR, Kepler TB, Zhang R, Moody MA, Haynes BF, Liao HX, Shaw DE, Harrison SC. Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody. Proc Natl Acad Sci U S A. 2013 Jan 2; 110(1):264-9.
    View in: PubMed
  14. Manolopoulou I, Kepler TB, Merl DM. Mixtures of Gaussian Wells: Theory, Computation, and Application. Comput Stat Data Anal. 2012 Dec 1; 56(12):3809-3820.
    View in: PubMed
  15. Haynes BF, Kelsoe G, Harrison SC, Kepler TB. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat Biotechnol. 2012 May; 30(5):423-33.
    View in: PubMed
  16. Bonsignori M, Montefiori DC, Wu X, Chen X, Hwang KK, Tsao CY, Kozink DM, Parks RJ, Tomaras GD, Crump JA, Kapiga SH, Sam NE, Kwong PD, Kepler TB, Liao HX, Mascola JR, Haynes BF. Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design. J Virol. 2012 Apr; 86(8):4688-92.
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  17. Moody MA, Zhang R, Walter EB, Woods CW, Ginsburg GS, McClain MT, Denny TN, Chen X, Munshaw S, Marshall DJ, Whitesides JF, Drinker MS, Amos JD, Gurley TC, Eudailey JA, Foulger A, DeRosa KR, Parks R, Meyerhoff RR, Yu JS, Kozink DM, Barefoot BE, Ramsburg EA, Khurana S, Golding H, Vandergrift NA, Alam SM, Tomaras GD, Kepler TB, Kelsoe G, Liao HX, Haynes BF. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PLoS One. 2011; 6(10):e25797.
    View in: PubMed
  18. Liao HX, Chen X, Munshaw S, Zhang R, Marshall DJ, Vandergrift N, Whitesides JF, Lu X, Yu JS, Hwang KK, Gao F, Markowitz M, Heath SL, Bar KJ, Goepfert PA, Montefiori DC, Shaw GC, Alam SM, Margolis DM, Denny TN, Boyd SD, Marshal E, Egholm M, Simen BB, Hanczaruk B, Fire AZ, Voss G, Kelsoe G, Tomaras GD, Moody MA, Kepler TB, Haynes BF. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med. 2011 Oct 24; 208(11):2237-49.
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  19. Morris L, Chen X, Alam M, Tomaras G, Zhang R, Marshall DJ, Chen B, Parks R, Foulger A, Jaeger F, Donathan M, Bilska M, Gray ES, Abdool Karim SS, Kepler TB, Whitesides J, Montefiori D, Moody MA, Liao HX, Haynes BF. Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. PLoS One. 2011; 6(9):e23532.
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  20. Alam SM, Liao HX, Dennison SM, Jaeger F, Parks R, Anasti K, Foulger A, Donathan M, Lucas J, Verkoczy L, Nicely N, Tomaras GD, Kelsoe G, Chen B, Kepler TB, Haynes BF. Differential reactivity of germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation. J Virol. 2011 Nov; 85(22):11725-31.
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  21. Ma BJ, Alam SM, Go EP, Lu X, Desaire H, Tomaras GD, Bowman C, Sutherland LL, Scearce RM, Santra S, Letvin NL, Kepler TB, Liao HX, Haynes BF. Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies. PLoS Pathog. 2011 Sep; 7(9):e1002200.
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  22. Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, Dormitzer PR, Haynes BF, Walter EB, Moody MA, Kepler TB, Liao HX, Harrison SC. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 2011 Aug 23; 108(34):14216-21.
    View in: PubMed
  23. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, Marshall DJ, Crump JA, Kapiga SH, Sam NE, Sinangil F, Pancera M, Yongping Y, Zhang B, Zhu J, Kwong PD, O'Dell S, Mascola JR, Wu L, Nabel GJ, Phogat S, Seaman MS, Whitesides JF, Moody MA, Kelsoe G, Yang X, Sodroski J, Shaw GM, Montefiori DC, Kepler TB, Tomaras GD, Alam SM, Liao HX, Haynes BF. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol. 2011 Oct; 85(19):9998-10009.
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  24. Ciupe SM, De Leenheer P, Kepler TB. Paradoxical suppression of poly-specific broadly neutralizing antibodies in the presence of strain-specific neutralizing antibodies following HIV infection. J Theor Biol. 2011 May 21; 277(1):55-66.
    View in: PubMed
  25. Feng F, Sales AP, Kepler TB. A Bayesian approach for estimating calibration curves and unknown concentrations in immunoassays. Bioinformatics. 2011 Mar 1; 27(5):707-12.
    View in: PubMed
  26. Saunders KO, Ward-Caviness C, Schutte RJ, Freel SA, Overman RG, Thielman NM, Cunningham CK, Kepler TB, Tomaras GD. Secretion of MIP-1ß and MIP-1a by CD8(+) T-lymphocytes correlates with HIV-1 inhibition independent of coreceptor usage. Cell Immunol. 2011; 266(2):154-64.
    View in: PubMed
  27. Bennett KM, Scarborough JE, Pappas TN, Kepler TB. Patient socioeconomic status is an independent predictor of operative mortality. Ann Surg. 2010 Sep; 252(3):552-7; discussion 557-8.
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  28. Kepler TB, Sample C, Hudak K, Roach J, Haines A, Walsh A, Ramsburg EA. Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler. BMC Genomics. 2010; 11:444.
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  29. Tang H, Cao W, Kasturi SP, Ravindran R, Nakaya HI, Kundu K, Murthy N, Kepler TB, Malissen B, Pulendran B. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol. 2010 Jul; 11(7):608-17.
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  30. Sen D, Forrest L, Kepler TB, Parker I, Cahalan MD. Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants. Proc Natl Acad Sci U S A. 2010 May 4; 107(18):8334-9.
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  31. Koelle K, Khatri P, Kamradt M, Kepler TB. A two-tiered model for simulating the ecological and evolutionary dynamics of rapidly evolving viruses, with an application to influenza. J R Soc Interface. 2010 Sep 6; 7(50):1257-74.
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  32. Kraus VB, Kepler TB, Stabler T, Renner J, Jordan J. First qualification study of serum biomarkers as indicators of total body burden of osteoarthritis. PLoS One. 2010; 5(3):e9739.
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  33. Vincent BG, Young EF, Buntzman AS, Stevens R, Kepler TB, Tisch RM, Frelinger JA, Hess PR. Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. J Immunol. 2010 Apr 15; 184(8):4196-204.
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  34. Kepler TB, Crossman C, Cook-Deegan R. Metastasizing patent claims on BRCA1. Genomics. 2010 May; 95(5):312-4.
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  35. Munshaw S, Kepler TB. SoDA2: a Hidden Markov Model approach for identification of immunoglobulin rearrangements. Bioinformatics. 2010 Apr 1; 26(7):867-72.
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  36. Ji C, Merl D, Kepler TB, West M. Spatial Mixture Modelling for Unobserved Point Processes: Examples in Immunofluorescence Histology. Bayesian Anal. 2009 Dec 4; 4(2):297-316.
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  37. Li L, He Q, Garland A, Yi Z, Aybar LT, Kepler TB, Frelinger JA, Wang B, Tisch R. beta cell-specific CD4+ T cell clonotypes in peripheral blood and the pancreatic islets are distinct. J Immunol. 2009 Dec 1; 183(11):7585-91.
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  38. Ciupe SM, Devlin BH, Markert ML, Kepler TB. The dynamics of T-cell receptor repertoire diversity following thymus transplantation for DiGeorge anomaly. PLoS Comput Biol. 2009 Jun; 5(6):e1000396.
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  39. Volpe JM, Kepler TB. Genetic correlates of autoreactivity and autoreactive potential in human Ig heavy chains. Immunome Res. 2009; 5:1.
    View in: PubMed
  40. Liao HX, Levesque MC, Nagel A, Dixon A, Zhang R, Walter E, Parks R, Whitesides J, Marshall DJ, Hwang KK, Yang Y, Chen X, Gao F, Munshaw S, Kepler TB, Denny T, Moody MA, Haynes BF. High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J Virol Methods. 2009 Jun; 158(1-2):171-9.
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  41. Barefoot B, Thornburg NJ, Barouch DH, Yu JS, Sample C, Johnston RE, Liao HX, Kepler TB, Haynes BF, Ramsburg E. Comparison of multiple vaccine vectors in a single heterologous prime-boost trial. Vaccine. 2008 Nov 11; 26(48):6108-18.
    View in: PubMed
  42. Sales AP, Tomaras GD, Kepler TB. Improving peptide-MHC class I binding prediction for unbalanced datasets. BMC Bioinformatics. 2008; 9:385.
    View in: PubMed
  43. Chan C, Feng F, Ottinger J, Foster D, West M, Kepler TB. Statistical mixture modeling for cell subtype identification in flow cytometry. Cytometry A. 2008 Aug; 73(8):693-701.
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  44. Frelinger J, Kepler TB, Chan C. Flow: Statistics, visualization and informatics for flow cytometry. Source Code Biol Med. 2008; 3:10.
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  45. Riddle DS, Miller PJ, Vincent BG, Kepler TB, Maile R, Frelinger JA, Collins EJ. Rescue of cytotoxic function in the CD8alpha knockout mouse by removal of MHC class II. Eur J Immunol. 2008 Jun; 38(6):1511-21.
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  46. Mitha F, Lucas TA, Feng F, Kepler TB, Chan C. The Multiscale Systems Immunology project: software for cell-based immunological simulation. Source Code Biol Med. 2008; 3:6.
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  47. Buckley KM, Munshaw S, Kepler TB, Smith LC. The 185/333 gene family is a rapidly diversifying host-defense gene cluster in the purple sea urchin Strongylocentrotus purpuratus. J Mol Biol. 2008 Jun 13; 379(4):912-28.
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  48. Munshaw S, Kepler TB. An information-theoretic method for the treatment of plural ancestry in phylogenetics. Mol Biol Evol. 2008 Jun; 25(6):1199-208.
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  49. Volpe JM, Kepler TB. Large-scale analysis of human heavy chain V(D)J recombination patterns. Immunome Res. 2008; 4:3.
    View in: PubMed
  50. Ray S, Kepler TB. Amino acid biophysical properties in the statistical prediction of peptide-MHC class I binding. Immunome Res. 2007; 3:9.
    View in: PubMed
  51. Kepler TB, Chan C. Spatiotemporal programming of a simple inflammatory process. Immunol Rev. 2007 Apr; 216:153-63.
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  52. 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.
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  53. Chan C, Kepler TB. Computational immunology--from bench to virtual reality. Ann Acad Med Singapore. 2007 Feb; 36(2):123-7.
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  54. 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.
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  55. 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.
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  56. 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.
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  57. 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.
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  58. Volpe JM, Cowell LG, Kepler TB. SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations. Bioinformatics. 2006 Feb 15; 22(4):438-44.
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  59. Tomfohr J, Lu J, Kepler TB. Pathway level analysis of gene expression using singular value decomposition. BMC Bioinformatics. 2005; 6:225.
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  60. 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.
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  61. Lu J, Tomfohr JK, Kepler TB. Identifying differential expression in multiple SAGE libraries: an overdispersed log-linear model approach. BMC Bioinformatics. 2005; 6:165.
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  62. 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.
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  63. Kepler TB. Microsimulation of Inducible Reorganization in Immunity. Complex Systems Science in BioMedicine (International Topics in Biomedical Engineering), eds. TS Deisboeck, YJ Kresh. Plenum. US. 2005.
  64. Smith JT, Tomfohr JK, Wells MC, Beebe TP, Kepler TB, Reichert WM. Measurement of cell migration on surface-bound fibronectin gradients. Langmuir. 2004 Sep 14; 20(19):8279-86.
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  65. Zhang SM, Adema CM, Kepler TB, Loker ES. Diversification of Ig superfamily genes in an invertebrate. Science. 2004 Jul 9; 305(5681):251-4.
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  66. 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.
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  67. 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.
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  68. 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.
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  69. 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.
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  70. 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.
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  71. 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.
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  72. Morgan KT, Ni H, Brown HR, Yoon L, Qualls CW, 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.
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  73. 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.
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  74. Sole RV, R Pastor-Satorras, DE Smith, and TB Kepler. A Model of Large-Scale Proteome Evolution. Adv. Complex Sys. 2002; 5:43-54.
  75. McLain JET, TB Kepler and D Ahmann. (2002) Factors Influencing Methane Consumption in a Temperate Coniferous Forest Soil under Elevated Atmospheric CO2: A Field Study. Global Biogeochemical Cycles 10.1029/2001GB001439. . Factors Influencing Methane Consumption in a Temperate Coniferous Forest Soil under Elevated Atmospheric CO2: A Field Study. Global Biogeochemical Cycles. 2002; (10.1029):10.1029/2001GB001439.
  76. Zavolan M, Kepler TB. Statistical inference of sequence-dependent mutation rates. Curr Opin Genet Dev. 2001 Dec; 11(6):612-5.
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  77. Kepler TB, Elston TC. Stochasticity in transcriptional regulation: origins, consequences, and mathematical representations. Biophys J. 2001 Dec; 81(6):3116-36.
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  78. Buchman TG, Cobb JP, Lapedes AS, Kepler TB. Complex systems analysis: a tool for shock research. Shock. 2001 Oct; 16(4):248-51.
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  79. 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.
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  80. 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.
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  81. 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.
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  82. 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.
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  83. Elston T and TB Kepler. A linear two-state model with complex dynamics. Phys. Lett. A. 2001; 280:204-208.
  84. 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.
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  85. 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.
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  86. 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.
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  87. 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.
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  88. 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.
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  89. 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.
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  90. 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.
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  91. 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.
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  92. 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.
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  93. 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.
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  94. 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.
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  95. 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.
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  96. Kepler TB, Bartl S. Plasticity under somatic mutation in antigen receptors. Curr Top Microbiol Immunol. 1998; 229:149-62.
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  97. Kepler TB. Codon bias and plasticity in immunoglobulins. Mol Biol Evol. 1997 Jun; 14(6):637-43.
    View in: PubMed
  98. Kepler TB. Oligomerization and PrPSc Stability in Prion Propagation: A Mathematical Analysis. Advances in Mathematical Population Dynamics: Molecules, Cells and Man, Eds. O. Arino, D. Axelrod and M. Kimmel. World Scientific. Singapore. 1997.
  99. 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.
    View in: PubMed
  100. 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.
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  101. 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.
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  102. Kelsoe G, B Zeng, TB Kepler. Do T-cells hypermutate?. Nature. 1995; 375:286 (Scientific Correspondence.
  103. Perelson AS and TB Kepler. The immune system as a complex system: Adaptation by somatic mutation. Chaos & Complexity 93, J. Tran Tranh Van, P. Berge, R. Conte and M. Dubois, eds. Editiones Frontieres. Gif-sur-Yvette, France. 1995; pp 97-106.
  104. Kepler TB, Perelson AS. Somatic hypermutation in B cells: an optimal control treatment. J Theor Biol. 1993 Sep 7; 164(1):37-64.
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  105. 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.
    View in: PubMed
  106. Kepler TB, Marder E. Spike initiation and propagation on axons with slow inward currents. Biol Cybern. 1993; 68(3):209-14.
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  107. Marder E, LF Abbott, F Buchholtz, IR Epstein, J Golowasch, SL Hooper and TB Kepler . Physiological insights from cellular and network models of the stomatogastric nervous system of lobsters and crabs. Am. Zool. 1993; 33:29-39.
  108. Kepler TB (1992). Geometric phases in dissipative classical systems. Mod. Phys. Lett. 1992; 6:1613-1622.
  109. Kepler TB, Abbott LF, Marder E. Reduction of conductance-based neuron models. Biol Cybern. 1992; 66(5):381-7.
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  110. Marder E, JM Weimann, TB Kepler and LF Abbott. Computational implications of a serotonin-sensitive region of axonal membrane on a dual-function motor neuron. Analysis and Modeling of Neural Systems II, F Eeckman, ed. Kluwer Academic Press. Norwell. 1992; pp. 377-390.
  111. Kepler TB, Kagan ML, Epstein IR. Geometric phases in dissipative systems. Chaos. 1991 Dec; 1(4):455-461.
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  112. Kepler TB, Kagan ML. Geometric phase shifts under adiabatic parameter changes in classical dissipative systems. Phys Rev Lett. 1991 Feb 18; 66(7):847-849.
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  113. Kagan ML, Kepler TB, Epstein IR. Geometric phase shifts in chemical oscillators. Nature. 1991 Feb 7; 349(6309):506-8.
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  114. Kepler TB, LF Abbott and E Marder. Order reduction for dynamical systems describing the behavior of complex neurons. Advances in Neural Information Processing Systems 3, RP Lippmann, JE Moody and DS Touretzky, eds. Morgan Kaufmann. San Mateo. 1991.
  115. Alexander HR, Jensen JC, Doherty GM, Block MI, Buresh CM, Norton JA. Induction of manganous superoxide dismutase (MnSOD) gene expression by interleukin-1 (IL-1): possible molecular basis for IL-1 protection against experimental sepsis. Surg Forum. 1991; 42:98-100.
  116. 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.
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  117. Abbott LF and TB Kepler. Model neurons: from Hodgkin-Huxley to Hopfield. Statistical Mechanics of Neural Networks, L Garrido, ed. Springer-Verlag. Berlin. 1990.
  118. Kepler TB (1990). Domains of attraction and the density of static metastable states in single-pattern iterated neural networks. J. Phys. A: Math. Gen. 1990; 24:1083-1092.
  119. Marder E, LF Abbott, TB Kepler and S Hooper. Modification of oscillator function by electrically coupled neurons. Induced Rhythmicities in the Brain, T Bullock and E Basar, eds. Birkhauser. Boston. 1990.
  120. Alexander HR, Langstein HN, Doherty GM, Jensen JC, Norton JA. Human recombinant tumor necrosis factor (hrTNF) protection against endotoxin induced shock and lethality in the rat. Surg Forum. 1990; 41:103-105.
  121. Kepler TB, S Datt, RB Meyer and LF Abbott. Chaos in a neural network circuit. Physica D. 1990; 46:449-457.
  122. Abbott LF and TB Kepler. Optimal learning in neural network memories. J Phys A: Math. Gen. 1989; 22:L711-L717.
  123. Abbott LF and TB Kepler. Universality in the space of interactions for network models. J. Phys. A: Math. Gen. 1989; 22:2031-2038.
  124. Kepler TB and LF Abbott. Domains of attraction in neural networks. J. Phys. France. 1988; 49:1657-1662.
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