The promise and challenge of high-throughput sequencing of the antibody repertoire

George Georgiou; Gregory C Ippolito; John Beausang; Christian E Busse; Hedda Wardemann; Stephen R Quake

doi:10.1038/nbt.2782

The promise and challenge of high-throughput sequencing of the antibody repertoire

Nat Biotechnol. 2014 Feb;32(2):158-68. doi: 10.1038/nbt.2782. Epub 2014 Jan 19.

Authors

George Georgiou¹, Gregory C Ippolito², John Beausang³, Christian E Busse⁴, Hedda Wardemann⁴, Stephen R Quake⁵

Affiliations

¹ 1] Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA. [2] Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA. [3] Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA. [4] Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
² 1] Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA. [2] Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas, USA.
³ 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
⁴ Max Planck Institute for Infection Biology, Berlin, Germany.
⁵ 1] Department of Bioengineering, Stanford University, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University, Stanford, California, USA. [3] Biophysics Graduate Program, Stanford University, Stanford, California, USA. [4] Department of Applied Physics, Stanford University, Stanford, California, USA.

Abstract

Efforts to determine the antibody repertoire encoded by B cells in the blood or lymphoid organs using high-throughput DNA sequencing technologies have been advancing at an extremely rapid pace and are transforming our understanding of humoral immune responses. Information gained from high-throughput DNA sequencing of immunoglobulin genes (Ig-seq) can be applied to detect B-cell malignancies with high sensitivity, to discover antibodies specific for antigens of interest, to guide vaccine development and to understand autoimmunity. Rapid progress in the development of experimental protocols and informatics analysis tools is helping to reduce sequencing artifacts, to achieve more precise quantification of clonal diversity and to extract the most pertinent biological information. That said, broader application of Ig-seq, especially in clinical settings, will require the development of a standardized experimental design framework that will enable the sharing and meta-analysis of sequencing data generated by different laboratories.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Biomedical Research
High-Throughput Nucleotide Sequencing*
Humans
Immunoglobulins* / chemistry
Immunoglobulins* / genetics
Immunologic Techniques
Mice
Models, Immunological

Substances

Immunoglobulins

Abstract

Publication types

MeSH terms

Substances

Grants and funding