title: Antibodyomics: bioinformatics technologies for understanding B-cell immunity to HIV-1.
abstract: Numerous antibodies have been identified from HIV-1-infected donors that neutralize diverse strains of HIV-1. These antibodies may provide the basis for a B cell-mediated HIV-1 vaccine. However, it has been unclear how to elicit similar antibodies by vaccination. To address this issue, we have undertaken an informatics-based approach to understand the genetic and immunologic processes controlling the development of HIV-1-neutralizing antibodies. As DNA sequencing comprises the fastest growing database of biological information, we focused on incorporating next-generation sequencing of B-cell transcripts to determine the origin, maturation pathway, and prevalence of broadly neutralizing antibody lineages (Antibodyomics1, 2, 4, and 6). We also incorporated large-scale robotic analyses of serum neutralization to identify and quantify neutralizing antibodies in donor cohorts (Antibodyomics3). Statistical analyses furnish another layer of insight (Antibodyomics5), with physical characteristics of antibodies and their targets through molecular dynamics simulations (Antibodyomics7) and free energy perturbation analyses (Antibodyomics8) providing information-rich output. Functional interrogation of individual antibodies (Antibodyomics9) and synthetic antibody libraries (Antibodyomics10) also yields multi-dimensional data by which to understand and improve antibodies. Antibodyomics, described here, thus comprise resolution-enhancing tools, which collectively embody an information-driven discovery engine aimed toward the development of effective B cell-based vaccines.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.|Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gwo-Yu
authors.initials: GY
authors.lastname: Chuang
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: DeKosky
authors.affiliation: Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Gindin
authors.affiliation: Vanderbilt Vaccine Center and Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lemmin
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.|Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.|Department of Systems Biology, Columbia University, New York, NY, USA.
authors.forename: Chaim A
authors.initials: CA
authors.lastname: Schramm
authors.affiliation: Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.|Department of Systems Biology, Columbia University, New York, NY, USA.
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Cinque
authors.initials: C
authors.lastname: Soto
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: An-Suei
authors.initials: AS
authors.lastname: Yang
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.|Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, USA.|Department of Systems Biology, Columbia University, New York, NY, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D019295:Computational Biology; D015483:HIV Antibodies / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: B-cell ontogeny; HIV vaccine; bioinformatics; broadly neutralizing antibodies; information technology; massively parallel sequencing