Abstract
In the decade since the human genome sequence was declared complete, the development of next generation sequencing (NGS) or “deep” sequencing to deliver cost-effective genomic sequencing has influenced advances beyond its primary application and changed the research landscape in many other areas. This review will survey recent applications of NGS which have broadened the understanding of natural antibody repertoires (the “antibodyome”) and how these evolve in response to viral infection. We will also report examples where deep sequencing of binding populations, derived from both natural and synthetic repertoires, have been used to benefit antibody engineering. This knowledge will ultimately lead to the design of more effective biological drugs and vaccines.
Highlights
Since the human genome was declared complete in April 2003, the costs of genomic sequencing have been reduced by orders of magnitude and available tools exist for data analysis, so that access to massively parallel sequencing is no longer the exclusive realm of large genome centers
We will concentrate on how next generation sequencing (NGS) informs our knowledge of natural antibody repertoires and how the humoral immune system adapts to infection, how it can be used to improve the efficiency of screening and how it can be applied to the design of new systems for the discovery of novel biologics
A proteomics approach that combines high resolution LCMS/multiple sclerosis (MS) analysis of purified and digested fragments of serum antibodies referenced against databases derived from the NGS reads of the B cell repertoire has been developed to provide more precise information for VH:VL pairing [32]
Summary
Since the human genome was declared complete in April 2003, the costs of genomic sequencing have been reduced by orders of magnitude and available tools exist for data analysis, so that access to massively parallel sequencing is no longer the exclusive realm of large genome centers. The diversity of the antibodyome in adult humans is estimated from the numbers of antibody expressing B cells within the body which is approximately 1010–1011. This population changes quickly with time and tissue distribution, resulting from daily turnover and replenishment of B cells, which potentially introduces new sequences [8]. This sequence multiplicity is due to several natural mechanisms, the most important being somatic recombination and rearrangement of two or three sets of gene segments into a single unique gene. In contrast to the CDR-H3 repertoire, recent investigation in the rearrangement in the light chain CDR-L3 found that a surprisingly large proportion of CDR-L3 (more than 20%) was shared across individuals, which indicates that an www.frontiersin.org
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