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B-cell repertoires are characterized by a diverse set of receptors ofdistinct specificities generated through two processes of somaticdiversification: V(D)J recombination and somatic hypermutations. B cell clonalfamilies stem from the same V(D)J recombination event, but differ in theirhypermutations. Clonal families identification is key to understanding B-cellrepertoire function, evolution and dynamics. We present HILARy (High-precisionInference of Lineages in Antibody Repertoires), an efficient, fast and precisemethod to identify clonal families from high-throughput sequencing datasets.HILARy combines probabilistic models that capture the receptor generation andselection statistics with adapted clustering methods to achieve consistentlyhigh inference accuracy. It automatically leverages the phylogenetic signal ofshared mutations in difficult repertoire subsets. Exploiting the highsensitivity of the method, we find the statistics of evolutionary propertiessuch as the site frequency spectrum and dN/dS ratio do not depend on thejunction length. We also identify a broad range of selection pressures scanningtwo orders of magnitude.

Combining mutation and recombination statistics to infer clonal families in antibody repertoires