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Using B cell receptor lineage structures to predict affinity

Authors: Duncan K. Ralph; Frederick A. Matsen IV;

Using B cell receptor lineage structures to predict affinity

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 .

Keywords

B-Lymphocytes, QH301-705.5, Decision Trees, Antibody Affinity, Populations and Evolution (q-bio.PE), Computational Biology, High-Throughput Nucleotide Sequencing, Receptors, Antigen, B-Cell, Antigen-Antibody Reactions, Evolution, Molecular, Machine Learning, FOS: Biological sciences, Consensus Sequence, Humans, Cell Lineage, Computer Simulation, Amino Acid Sequence, Biology (General), Quantitative Biology - Populations and Evolution, Phylogeny, Research Article

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selected citations
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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