A Bayesian phylogenetic hidden Markov model for B cell receptor sequence analysis.
| Autor: | Dhar A; Department of Statistics, University of Washington, Seattle, Washington, United States of America.; Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Ralph DK; Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America., Minin VN; Department of Statistics, University of California, Irvine, California, United States of America., Matsen FA 4th; Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. |
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| Jazyk: | angličtina |
| Zdroj: | PLoS computational biology [PLoS Comput Biol] 2020 Aug 17; Vol. 16 (8), pp. e1008030. Date of Electronic Publication: 2020 Aug 17 (Print Publication: 2020). |
| DOI: | 10.1371/journal.pcbi.1008030 |
| Abstrakt: | The human body generates a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design vaccines for highly mutable pathogens such as influenza and HIV. BCR diversity is induced by naturally occurring combinatorial "V(D)J" rearrangement, mutation, and selection processes. Most current methods for BCR sequence analysis focus on separately modeling the above processes. Statistical phylogenetic methods are often used to model the mutational dynamics of BCR sequence data, but these techniques do not consider all the complexities associated with B cell diversification such as the V(D)J rearrangement process. In particular, standard phylogenetic approaches assume the DNA bases of the progenitor (or "naive") sequence arise independently and according to the same distribution, ignoring the complexities of V(D)J rearrangement. In this paper, we introduce a novel approach to Bayesian phylogenetic inference for BCR sequences that is based on a phylogenetic hidden Markov model (phylo-HMM). This technique not only integrates a naive rearrangement model with a phylogenetic model for BCR sequence evolution but also naturally accounts for uncertainty in all unobserved variables, including the phylogenetic tree, via posterior distribution sampling. Competing Interests: The authors have declared that no competing interests exist. |
| Databáze: | MEDLINE |
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