Abstract

We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in patients that have recovered. There exist effective experimental methods of accomplishing this, such as cell sorting and baiting; however they are time consuming and expensive. Next generation sequencing of B cell receptor (BCR) repertoires offers an additional source of sequences that could be tapped if we had a reliable method of selecting those coding for the best antibodies. In this paper we introduce a method that uses evolutionary information from the family of related sequences that share a naive ancestor to predict the affinity of each resulting antibody for its antigen. When combined with information on the identity of the antigen, this method should provide a source of effective new antibodies. We also introduce a method for a related task: given an antibody of interest and its inferred ancestral lineage, which branches in the tree are likely to harbor key affinity-increasing mutations? We evaluate the performance of these methods on a wide variety of simulated samples, as well as two real data samples. These methods are implemented as part of continuing development of the partis BCR inference package, available at https://github.com/psathyrella/partis. Comments Please post comments or questions on this paper as new issues at https://git.io/Jvxkn.

Highlights

  • Antibodies are the foundation of both vaccine-induced immunity and many important therapeutics

  • Generation sequencing of the B cell receptor (BCR) repertoire provides a broad and highly informative view of the DNA sequences from which antibodies arise

  • In this paper we introduce new computational methods that use evolutionary information from the family of related BCR sequences to predict the affinity of each resulting antibody for its corresponding foreign antigen

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Summary

Introduction

Antibodies are the foundation of both vaccine-induced immunity and many important therapeutics They stem from B cells through the processes of VDJ rearrangement and somatic hypermutation (SHM), which yield a vast repertoire of B cell receptors (BCRs) within each person. There exist several effective experimental methods of finding high affinity B cells. Both cell sorting and antigen baiting have been used to find a variety of important antibodies [2,3,4]. Constructing a stable baiting antigen for certain conformational epitopes can be challenging. Their main limitation is that they require large investments of time and resources

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