Using B cell receptor lineage structures to predict affinity

PLoS Comput Biol. 2020 Nov 11;16(11):e1008391. doi: 10.1371/journal.pcbi.1008391. eCollection 2020 Nov.

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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibody Affinity*
  • Antigen-Antibody Reactions
  • B-Lymphocytes / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Computational Biology
  • Computer Simulation
  • Consensus Sequence
  • Decision Trees
  • Evolution, Molecular
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Machine Learning
  • Phylogeny
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / genetics*
  • Receptors, Antigen, B-Cell / immunology*

Substances

  • Receptors, Antigen, B-Cell