Please use this identifier to cite or link to this item:
https://doi.org/10.21256/zhaw-3886| Publication type: | Article in scientific journal |
| Type of review: | Peer review (publication) |
| Title: | Antibody-specific model of amino acid substitution for immunological inferences from alignments of antibody sequences |
| Authors: | Mirsky, Alexander Anisimova, Maria Kazandjian, Linda |
| DOI: | 10.21256/zhaw-3886 10.1093/molbev/msu340 |
| Published in: | Molecular Biology and Evolution |
| Volume(Issue): | 32 |
| Issue: | 3 |
| Page(s): | 806 |
| Pages to: | 819 |
| Issue Date: | 2014 |
| Publisher / Ed. Institution: | Oxford University Press |
| ISSN: | 0737-4038 1537-1719 |
| Language: | English |
| Subjects: | Markov model; Amino acid substitution; Alignment; Evolution; Antibody; Somatic hypermutation; Antibody genealogy |
| Subject (DDC): | 572: Biochemistry |
| Abstract: | Antibodies are glycoproteins produced by the immune system as a dynamically adaptive line of defense against invading pathogens. Very elegant and specific mutational mechanisms allow B lymphocytes to produce a large and diversified repertoire of antibodies, which is modified and enhanced throughout all adulthood. One of these mechanisms is somatic hypermutation, which stochastically mutates nucleotides in the antibody genes, forming new sequences with different properties and, eventually, higher affinity and selectivity to the pathogenic target. Since somatic hypermutation involves fast mutation of antibody sequences, this process can be described using a Markov substitution model of molecular evolution. Here, using large sets of antibody sequences from mice and humans, we infer an empirical amino acid substitution model AB, which is specific to antibody sequences. Compared to existing general amino acid models, we show that the AB model provides significantly better description for the somatic evolution of mice and human antibody sequences, as demonstrated on large next generation sequencing (NGS) antibody data. General amino acid models are reflective of conservation at the protein level due to functional constraints, with most frequent amino acids exchanges taking place between residues with the same or similar physicochemical properties. In contrast, within the variable part of antibody sequences we observed an elevated frequency of exchanges between amino acids with distinct physicochemical properties. This is indicative of a sui generis mutational mechanism, specific to antibody somatic hypermutation. We illustrate this property of antibody sequences by a comparative analysis of the network modularity implied by the AB model and general amino acid substitution models. We recommend using the new model for computational studies of antibody sequence maturation, including inference of alignments and phylogenetic trees describing antibody somatic hypermutation in large NGS data sets. The AB model is implemented in the open-source software CodonPhyML (http://sourceforge.net/projects/codonphyml) and can be downloaded and supplied by the user to ProGraphMSA (http://sourceforge.net/projects/prographmsa) or other alignment and phylogeny reconstruction programs that allow for user-defined substitution models. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/8270 |
| Fulltext version: | Published version |
| License (according to publishing contract): | CC BY 4.0: Attribution 4.0 International |
| Departement: | Life Sciences and Facility Management |
| Organisational Unit: | Institute of Computational Life Sciences (ICLS) |
| Appears in collections: | Publikationen Life Sciences und Facility Management |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| msu340.pdf | 593.17 kB | Adobe PDF |  View/Open |
Show full item record
Mirsky, A., Anisimova, M., & Kazandjian, L. (2014). Antibody-specific model of amino acid substitution for immunological inferences from alignments of antibody sequences. Molecular Biology and Evolution, 32(3), 806–819. https://doi.org/10.21256/zhaw-3886
Mirsky, A., Anisimova, M. and Kazandjian, L. (2014) ‘Antibody-specific model of amino acid substitution for immunological inferences from alignments of antibody sequences’, Molecular Biology and Evolution, 32(3), pp. 806–819. Available at: https://doi.org/10.21256/zhaw-3886.
A. Mirsky, M. Anisimova, and L. Kazandjian, “Antibody-specific model of amino acid substitution for immunological inferences from alignments of antibody sequences,” Molecular Biology and Evolution, vol. 32, no. 3, pp. 806–819, 2014, doi: 10.21256/zhaw-3886.
MIRSKY, Alexander, Maria ANISIMOVA und Linda KAZANDJIAN, 2014. Antibody-specific model of amino acid substitution for immunological inferences from alignments of antibody sequences. Molecular Biology and Evolution. 2014. Bd. 32, Nr. 3, S. 806–819. DOI 10.21256/zhaw-3886
Mirsky, Alexander, Maria Anisimova, and Linda Kazandjian. 2014. “Antibody-Specific Model of Amino Acid Substitution for Immunological Inferences from Alignments of Antibody Sequences.” Molecular Biology and Evolution 32 (3): 806–19. https://doi.org/10.21256/zhaw-3886.
Mirsky, Alexander, et al. “Antibody-Specific Model of Amino Acid Substitution for Immunological Inferences from Alignments of Antibody Sequences.” Molecular Biology and Evolution, vol. 32, no. 3, 2014, pp. 806–19, https://doi.org/10.21256/zhaw-3886.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.