Inferring B cell specificity for vaccines using a Bayesian mixture model

Fowler, Anna; Galson, Jacob D.; Trück, Johannes; Kelly, Dominic F.; Lunter, Gerton

doi:10.1186/s12864-020-6571-7

Cited by 7 publications

(4 citation statements)

References 23 publications

(36 reference statements)

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“…Estimated hypothetical total diversity is estimated to be $1 Â 10 140 total unique CDR3 sequences (18). However, the functional diversity is much more highly restricted to around 1 Â 10 13 to 1 Â 10 18 because of the V-, D-, and J-gene segments that create the CDR3 backbone (12,27) and because mice only have $1 Â 10 8 B cells, many of the potential CDR3s are never seen in the repertoire (15) In our unamplified individual mouse spleen samplings, there is an average of $3000 unique CDR3s that are not found in any other mouse. This might translate to $30,000 unique CDR3s if we assume we are assessing 10% of the repertoire or 300,000 unique CDR3s if that amplification is only 1% of the repertoire compared with what we might see if we amplified the sequencing.…”

Section: Discussionmentioning

confidence: 99%

An Analysis of the Effects of Spaceflight and Vaccination on Antibody Repertoire Diversity

et al. 2021

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Ab repertoire diversity plays a critical role in the hosts ability to fight pathogens. CDR3 is partially responsible for Ab-Ag binding and is a significant source of diversity in the repertoire. CDR3 diversity is generated during VDJ rearrangement because of gene segment selection, gene segment trimming and splicing, and the addition of nucleotides. We analyzed the Ab repertoire diversity across multiple experiments examining the effects of spaceflight on the Ab repertoire after vaccination. Five datasets from four experiments were analyzed using rank-abundance curves and Shannon indices as measures of diversity. We discovered a trend toward lower diversity as a result of spaceflight but did not find the same decrease in our physiological model of microgravity in either the spleen or bone marrow. However, the bone marrow repertoire showed a reduction in diversity after vaccination. We also detected differences in Shannon indices between experiments and tissues. We did not detect a pattern of CDR3 usage across the experiments. Overall, we were able to find differences in the Ab repertoire diversity across experimental groups and tissues. ImmunoHorizons, 2021, 5: 675-686.

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Section: Discussionmentioning

confidence: 99%

An Analysis of the Effects of Spaceflight and Vaccination on Antibody Repertoire Diversity

et al. 2021

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“…With longitudinal sampling, a family’s persistence over time can be a strong indicator of specificity in the presence of either chronic infection [ 53 ] or the application of multiple vaccinations [ 49 ]. With several subjects that have been exposed to the same antigen, we can select shared lineages either using simple sequence similarity [ 46 – 48 , 54 ] or a Bayesian mixture model incorporating also clonal abundance [ 55 ]. With an outside source of antigen-specific sequences (e.g.…”

Section: Discussionmentioning

confidence: 99%

Using B cell receptor lineage structures to predict affinity

Ralph¹,

Matsen²

2020

PLoS Comput Biol

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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.

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“…With longitudinal sampling, a family's persistence over time can be a strong indicator of specificity in the presence of either chronic infection [53] or the application of multiple vaccinations [49]. With several subjects that have been exposed to the same antigen, we can select shared lineages either using simple sequence similarity [46][47][48]54] or a Bayesian mixture model incorporating also clonal abundance [55]. With an outside source of antigen-specific sequences (e.g.…”

Section: Discussionmentioning

confidence: 99%

Using B cell receptor lineage structures to predict affinity

Ralph

Matsen

2020

Preprint

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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? 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.

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Inferring B cell specificity for vaccines using a Bayesian mixture model

Cited by 7 publications

References 23 publications

An Analysis of the Effects of Spaceflight and Vaccination on Antibody Repertoire Diversity

An Analysis of the Effects of Spaceflight and Vaccination on Antibody Repertoire Diversity

Using B cell receptor lineage structures to predict affinity

Using B cell receptor lineage structures to predict affinity

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