Next-generation sequencing and protein mass spectrometry for the comprehensive analysis of human cellular and serum antibody repertoires
JJ Lavinder, AP Horton, G Georgiou… - Current opinion in …, 2015 - Elsevier
Current opinion in chemical biology, 2015•Elsevier
Highlights•Next-generation sequencing of peripheral B cells (BCR-seq) in health and
disease states.•Serum antibody proteomics (Ig-seq) complements BCR-seq in analyzing
endpoint functionality.•Advances in the pairing and NGS of antibody heavy chain and light
chain (VH: VL) sequences.•Combined, BCR-seq and Ig-seq provide a clear advance in
antibody discovery.Recent developments of high-throughput technologies are enabling the
molecular-level analysis and bioinformatic mining of antibody-mediated (humoral) immunity …
disease states.•Serum antibody proteomics (Ig-seq) complements BCR-seq in analyzing
endpoint functionality.•Advances in the pairing and NGS of antibody heavy chain and light
chain (VH: VL) sequences.•Combined, BCR-seq and Ig-seq provide a clear advance in
antibody discovery.Recent developments of high-throughput technologies are enabling the
molecular-level analysis and bioinformatic mining of antibody-mediated (humoral) immunity …
Highlights
- Next-generation sequencing of peripheral B cells (BCR-seq) in health and disease states.
- Serum antibody proteomics (Ig-seq) complements BCR-seq in analyzing endpoint functionality.
- Advances in the pairing and NGS of antibody heavy chain and light chain (VH: VL) sequences.
- Combined, BCR-seq and Ig-seq provide a clear advance in antibody discovery.
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).
Elsevier