Empirical substitution models across positions and genetic organization hierarchy for antibodies

ABSTRACT: Phylogenetic substitution models, such as continuous-time Markov chains, are widely employed in phylogenetics and comparative analysis to describe the rates of amino-acid changes over time. These models rely on the assumption of a steady evolutionary process, which is often valid for many protein families, enabling their successful application across diverse contexts. However, this assumption is violated in cases of non-steady evolutionary processes such as somatic hypermutation (SHM) in B-cells, where accelerated and targeted mutations occur. As a result, general substitution models derived from protein families may not accurately reflect the complexities of such processes. To address this limitation, we developed empirical substitution models specifically tailored to antibodies, which are subject to SHM. These models were constructed using a large repertoire of antibodies from the Open Antibody Space, providing a comprehensive dataset for model parameterisation. Furthermore, we constructed these models at multiple levels of genetic resolution, encompassing different regions and sites within the antibody, to capture the nuances of SHM. This approach enables a more detailed understanding of the evolutionary dynamics underlying antibody diversification.

ORGANISM(S): Homo sapiens

SUBMITTER: Bikash Kumar Bhandari 

PROVIDER: S-BSST2920 | biostudies-other |

SECONDARY ACCESSION(S): 10.5281/zenodo.19496397

REPOSITORIES: biostudies-other