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

By G. Georgiou, G. Ippolito, J. Beausang, C. E. Busse, Hedda Wardemann, Stephen R. Quake. Nature Biotechnology, 2014

643 citations recorded by the source corpus.

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.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/c9f2ba9d8fea3008779442c4ed578dfeb558fb66

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In Immunology

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation (2019, background): “An antibody molecule consists of two binding domains: the variable domain of the heavy chain (HC) and light chain (LC) that preferentially or collectively contribute to the binding affinity of the antibody towards the target antigen [52].”
Modeling and docking antibody structures with Rosetta (2017, background): “Next-generation sequencing techniques have enabled rapid determination of large numbers of antibody sequences 1 .”
VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires (2015, methodology): “In future we plan extending VDJtools software to address another highly important problem in the field, the analysis of antibody repertoire [70].”
Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires (2016, background): “However, because of technical limitations (13), these and other studies were confined to analysis of the heavy and light chain repertoires separately.”
Modern Hopfield Networks and Attention for Immune Repertoire Classification (2020, background): “The ability to sequence and analyze human immune receptors at large scale has led to fundamental and mechanistic insights into the adaptive immune system and has also opened the opportunity for the development of novel diagnostics and therapy approaches (Georgiou et al., 2014; Brown et al., 2019).”
Observed Antibody Space: A diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences (2021, background): “There are now tens of BCR-seq datasets available containing millions of sequences from a variety of different hosts, diseases, treatments, and cell types.(10) The use of data from multiple studies allows larger and more complete analyses to be carried out, but is hindered by nonstandard data formats”
Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies (2022, background): “Analyses of immune repertoires have traditionally been limited to sequence data alone 1 , as high-throughput antibody structure determination was experimentally prohibitive and prediction methods were too slow or inaccurate.”