  Somatic hypermutations of immunoglobulin (Ig) genes occuring during affinity
maturation drive B-cell receptors' ability to evolve strong binding to their
antigenic targets. The landscape of these mutations is highly heterogeneous,
with certain regions of the Ig gene being preferentially targeted. However, a
rigorous quantification of this bias has been difficult because of phylogenetic
correlations between sequences and the interference of selective forces. Here,
we present an approach that corrects for these issues, and use it to learn a
model of hypermutation preferences from a recently published large IgH
repertoire dataset. The obtained model predicts mutation profiles accurately
and in a reproducible way, including in the previously uncharacterized
Complementarity Determining Region 3, revealing that both the sequence context
of the mutation and its absolute position along the gene are important. In
addition, we show that hypermutations occurring concomittantly along B-cell
lineages tend to co-localize, suggesting a possible mechanism for accelerating
affinity maturation.
