title: Next-generation sequencing and protein mass spectrometry for the comprehensive analysis of human cellular and serum antibody repertoires.
abstract: Recent developments of high-throughput technologies are enabling the molecular-level analysis and bioinformatic mining of antibody-mediated (humoral) immunity in humans at an unprecedented level. These approaches explore either the sequence space of B-cell receptor repertoires using next-generation deep sequencing (BCR-seq), or the amino acid identities of antibody in blood using protein mass spectrometry (Ig-seq), or both. Generalizable principles about the molecular composition of the protective humoral immune response are being defined, and as such, the field could supersede traditional methods for the development of diagnostics, vaccines, and antibody therapeutics. Three key challenges remain and have driven recent advances: (1) incorporation of innovative techniques for paired BCR-seq to ascertain the complete antibody variable-domain VH:VL clonotype, (2) integration of proteomic Ig-seq with BCR-seq to reveal how the serum antibody repertoire compares with the antibody repertoire encoded by circulating B cells, and (3) a demand to link antibody sequence data to functional meaning (binding and protection).
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1062, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Lavinder
authors.affiliation: Center for Systems & Synthetic Biology, University of Texas at Austin, Austin, TX 78712-1062, USA; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Horton
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1062, USA; Center for Systems & Synthetic Biology, University of Texas at Austin, Austin, TX 78712-1062, USA; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712-1062, USA.
authors.forename: George
authors.initials: G
authors.lastname: Georgiou
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712-1062, USA. Electronic address: gci@mail.utexas.edu.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ippolito
mesh_terms: D000906:Antibodies / Q000032:analysis* / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D040901:Proteomics / Q000379:methods
chemical_list: D000906:Antibodies