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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 .
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
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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