Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of Antibody Repertoires

Abs are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made Abs the primary class of biopharmaceuticals. Recently, it has become possible to query their immense natural diversity using next-generation sequencing of Ig gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 55 studies, covering more than half a billion Ab sequences across diverse immune states, organisms (primarily human and mouse), and individuals. We have sorted, cleaned, annotated, translated, and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at http://antibodymap.org. The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.

[1]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.

[2]  Sean R. Eddy,et al.  Multiple Alignment Using Hidden Markov Models , 1995, ISMB.

[3]  V. Giudicelli,et al.  IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. , 2003, Developmental and comparative immunology.

[4]  J. Engler,et al.  Expressed murine and human CDR-H3 intervals of equal length exhibit distinct repertoires that differ in their amino acid composition and predicted range of structures. , 2003, Journal of molecular biology.

[5]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[6]  Mathieu Rouard,et al.  IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. , 2005, Developmental and comparative immunology.

[7]  Marie-Paule Lefranc,et al.  IMGT , the international ImMunoGeneTics information system , 2003 .

[8]  H. Schroeder Similarity and divergence in the development and expression of the mouse and human antibody repertoires. , 2006, Developmental and comparative immunology.

[9]  Jan Berka,et al.  Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire , 2009, Proceedings of the National Academy of Sciences.

[10]  A. Torkamani,et al.  Regulation of the B Cell Receptor Repertoire and Self-Reactivity by BAFF , 2010, The Journal of Immunology.

[11]  Ying Cheng,et al.  The European Nucleotide Archive , 2010, Nucleic Acids Res..

[12]  Mario Roederer,et al.  Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing , 2011, Science.

[13]  Steven Salzberg,et al.  BIOINFORMATICS ORIGINAL PAPER , 2004 .

[14]  J. Mullikin,et al.  Somatic Populations of PGT135–137 HIV-1-Neutralizing Antibodies Identified by 454 Pyrosequencing and Bioinformatics , 2012, Front. Microbio..

[15]  Scott D Boyd,et al.  Convergent antibody signatures in human dengue. , 2013, Cell host & microbe.

[16]  Baoshan Zhang,et al.  Mining the antibodyome for HIV-1–neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains , 2013, Proceedings of the National Academy of Sciences.

[17]  Tongqing Zhou,et al.  De novo identification of VRC01 class HIV-1–neutralizing antibodies by next-generation sequencing of B-cell transcripts , 2013, Proceedings of the National Academy of Sciences.

[18]  R. Rance,et al.  Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations , 2013, Genome research.

[19]  George Georgiou,et al.  High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire , 2013, Nature Biotechnology.

[20]  G. Ippolito,et al.  Intrinsic bias and public rearrangements in the human immunoglobulin Vλ light chain repertoire , 2013, Genes and Immunity.

[21]  Mark M. Davis,et al.  Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination , 2013, Science Translational Medicine.

[22]  Young Do Kwon,et al.  Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. , 2013, Immunity.

[23]  Ning Ma,et al.  IgBLAST: an immunoglobulin variable domain sequence analysis tool , 2013, Nucleic Acids Res..

[24]  Chaim A. Schramm,et al.  Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus , 2013, Nature.

[25]  T. Kepler,et al.  Microbial colonization influences early B-lineage development in the gut lamina propria , 2013, Nature.

[26]  J. Mascola,et al.  Single-Cell and Deep Sequencing of IgG-Switched Macaque B Cells Reveal a Diverse Ig Repertoire following Immunization , 2014, The Journal of Immunology.

[27]  S. Durham,et al.  Rhinitis, sinusitis, and upper airway disease Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis , 2022 .

[28]  George Georgiou,et al.  Differences in the Composition of the Human Antibody Repertoire by B Cell Subsets in the Blood , 2014, Front. Immunol..

[29]  Sai T. Reddy,et al.  Comprehensive Evaluation and Optimization of Amplicon Library Preparation Methods for High-Throughput Antibody Sequencing , 2014, PloS one.

[30]  M. Sirota,et al.  Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis , 2014, Science Translational Medicine.

[31]  Steven H. Kleinstein,et al.  B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes , 2014, Science Translational Medicine.

[32]  Victor Greiff,et al.  Quantitative assessment of the robustness of next-generation sequencing of antibody variable gene repertoires from immunized mice , 2014, BMC Immunology.

[33]  J. Galson,et al.  Studying the antibody repertoire after vaccination: practical applications. , 2014, Trends in immunology.

[34]  Mark M. Davis,et al.  Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. , 2014, Cell host & microbe.

[35]  Chaim A. Schramm,et al.  Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies , 2014, Nature.

[36]  Jeffrey A. Wiser,et al.  ImmPort: disseminating data to the public for the future of immunology , 2014, Immunologic Research.

[37]  Enkelejda Miho,et al.  High-Throughput Sequencing of Human Immunoglobulin Variable Regions with Subtype Identification , 2014, PloS one.

[38]  S. Quake,et al.  The promise and challenge of high-throughput sequencing of the antibody repertoire , 2014, Nature Biotechnology.

[39]  Mikhail Shugay,et al.  Towards error-free profiling of immune repertoires , 2014, Nature Methods.

[40]  Young Do Kwon,et al.  Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection , 2015, Cell.

[41]  Lynn Morris,et al.  Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies , 2015, Nature Medicine.

[42]  V. Greiff,et al.  A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status , 2015, Genome Medicine.

[43]  Ivan V. Gregoretti,et al.  Diversity, cellular origin and autoreactivity of antibody-secreting cell expansions in acute Systemic Lupus Erythematosus , 2015, Nature Immunology.

[44]  George Georgiou,et al.  In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire , 2014, Nature Medicine.

[45]  Johannes Trück,et al.  BCR repertoire sequencing: different patterns of B cell activation after two Meningococcal vaccines , 2015, Immunology and cell biology.

[46]  Johannes Trück,et al.  Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences , 2015, EBioMedicine.

[47]  Hao Wu,et al.  Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. , 2015, Immunity.

[48]  Cinque S. Soto,et al.  Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors , 2015, Cell.

[49]  André Bleich,et al.  Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota , 2015, Nature Immunology.

[50]  Yan Wang,et al.  The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains , 2015, Philosophical Transactions of the Royal Society B: Biological Sciences.

[51]  Anna Tramontano,et al.  Tabhu: tools for antibody humanization , 2014, Bioinform..

[52]  Baoshan Zhang,et al.  Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination , 2016, Nature Medicine.

[53]  Johannes Trück,et al.  B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation , 2016, Genome Medicine.

[54]  Scott D Boyd,et al.  Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy. , 2016, The Journal of allergy and clinical immunology.

[55]  G. B. Karlsson Hedestam,et al.  Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity , 2016, Nature Communications.

[56]  Cinque S. Soto,et al.  Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses , 2016, Cell.

[57]  Tongqing Zhou,et al.  Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. , 2016, Immunity.

[58]  J. Galson,et al.  Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination , 2016, Scientific Reports.

[59]  Jian Wang,et al.  Comparative Analysis of Immune Repertoires between Bactrian Camel's Conventional and Heavy-Chain Antibodies , 2016, PloS one.

[60]  Charlotte M. Deane,et al.  ANARCI: antigen receptor numbering and receptor classification , 2015, Bioinform..

[61]  Cornelia L Dekker,et al.  Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells , 2016, Nature Communications.

[62]  K. Roskin,et al.  Defining antigen-specific plasmablast and memory B cell subsets in blood following viral infection and vaccination of humans , 2016, Nature Immunology.

[63]  Francois Vigneault,et al.  A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data , 2016, The Journal of Immunology.

[64]  Sai T Reddy,et al.  Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting , 2016, Science Advances.

[65]  Chaim A. Schramm,et al.  Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody , 2016, Cell.

[66]  Jeffrey J. Gray,et al.  Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires , 2016, Proceedings of the National Academy of Sciences.

[67]  Evgeny S. Egorov,et al.  High-quality full-length immunoglobulin profiling with unique molecular barcoding , 2016, Nature Protocols.

[68]  M. Arbabi-Ghahroudi Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook , 2017, Front. Immunol..

[69]  Cédric R. Weber,et al.  Learning the High-Dimensional Immunogenomic Features That Predict Public and Private Antibody Repertoires , 2017, The Journal of Immunology.

[70]  C. Deane,et al.  How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data , 2017, Front. Immunol..

[71]  D. Wesemann,et al.  IgH isotype-specific B cell receptor expression influences B cell fate , 2017, Proceedings of the National Academy of Sciences.

[72]  N. Chiorazzi,et al.  Novel Method for High-Throughput Full-Length IGHV-D-J Sequencing of the Immune Repertoire from Bulk B-Cells with Single-Cell Resolution , 2017, Front. Immunol..

[73]  Syed Ahmad Chan Bukhari,et al.  Adaptive Immune Receptor Repertoire Community recommendations for sharing immune-repertoire sequencing data , 2017, Nature Immunology.

[74]  Sai T Reddy,et al.  Advanced Methodologies in High-Throughput Sequencing of Immune Repertoires. , 2017, Trends in biotechnology.

[75]  Aaron M. Rosenfeld,et al.  An atlas of B-cell clonal distribution in the human body , 2017, Nature Biotechnology.

[76]  K Dane Wittrup,et al.  Biophysical properties of the clinical-stage antibody landscape , 2017, Proceedings of the National Academy of Sciences.

[77]  Joshua A. Mitchell,et al.  T-dependent B cell responses to Plasmodium induce antibodies that form a high-avidity multivalent complex with the circumsporozoite protein , 2017, PLoS pathogens.

[78]  Francois Vigneault,et al.  Hierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data , 2017, The Journal of Immunology.

[79]  Yali Qin,et al.  Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region. , 2017, Virology.

[80]  Ian M. Fingerman,et al.  Database resources of the National Center for Biotechnology Information , 2010, Nucleic Acids Res..

[81]  Theo M. Luider,et al.  Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics , 2017, Front. Immunol..

[82]  Cédric R. Weber,et al.  Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development. , 2017, Cell reports.

[83]  Julian Q. Zhou,et al.  Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing , 2017, The Journal of Immunology.

[84]  Syed Ahmad Chan Bukhari,et al.  Reproducibility and Reuse of Adaptive Immune Receptor Repertoire Data , 2017, Front. Immunol..

[85]  Fredrik Levander,et al.  Antibody-encoding repertoires of bone marrow and peripheral blood-a focus on IgE. , 2017, The Journal of allergy and clinical immunology.

[86]  John M. Fonner,et al.  VDJServer: A Cloud-Based Analysis Portal and Data Commons for Immune Repertoire Sequences and Rearrangements , 2018, Front. Immunol..

[87]  C. Glass,et al.  Massively Parallel Sequencing of Peritoneal and Splenic B Cell Repertoires Highlights Unique Properties of B-1 Cell Antibodies , 2018, The Journal of Immunology.

[88]  Cédric R. Weber,et al.  Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires , 2017, Front. Immunol..

[89]  Jamie K. Scott,et al.  iReceptor: A platform for querying and analyzing antibody/B‐cell and T‐cell receptor repertoire data across federated repositories , 2018, Immunological reviews.

[90]  Barry Smith,et al.  ImmPort, toward repurposing of open access immunological assay data for translational and clinical research , 2018, Scientific Data.

[91]  M. Pecaut,et al.  Characterization of the naive murine antibody repertoire using unamplified high-throughput sequencing , 2018, PloS one.

[92]  J. Reichert,et al.  Antibodies to watch in 2018 , 2018, mAbs.

[93]  Evan Bolton,et al.  Database resources of the National Center for Biotechnology Information , 2017, Nucleic Acids Res..

[94]  Johannes Trück,et al.  B‐cell receptor repertoire sequencing in patients with primary immunodeficiency: a review , 2018, Immunology.

[95]  Paul G. Thomas,et al.  Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination , 2022 .