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Statistical Mechanics in Systems Biology: Villa Orlandi, Anacapri ~ May 29 - June 1, 2012 |
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Aleksandra Walczak Laboratoire de Physique Theorique, Ecole Normale Superieure, Paris (France) Quantifying the diversity of antibody receptors Recognition of pathogens relies on families of proteins showing great diversity. I will show how one can construct probabilistic models of the sequence repertoire, building on recent experiments that provide a nearly exhaustive sampling of B-cell receptor sequences in zebrafish. Specifically I will focus on describing the diversity in the junctional regions, which is not possible to do by traditional alignement methods. By exploiting the interpretation of these models, I make several predictions for the collective properties of the sequence ensemble: the distribution of sequences obeys Zipf’s law (which states that the abundance of sequences decays as the inverse of their rank), the repertoire decomposes into several clusters, and there is a massive restriction of diversity because of the correlations. These predictions are completely inconsistent with models in which amino acid substitutions are made independently at each site and are in good agreement with the data. These results suggest that antibody diversity is not limited by the sequences encoded in the genome and may reflect rapid adaptation to antigenic challenges. I will finish by discussing probabilistic models that describe the generation of diversity in the junctional region. |
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