TRIBAL: Tree Inference of B cell Clonal Lineages.

B cells are a critical component of the adaptive immune system, responsible for producing antibodies that help protect the body from infections and foreign substances. Single cell RNA-sequencing (scRNA-seq) has allowed for both profiling of B cell receptor (BCR) sequences and gene expression. However, understanding the adaptive and evolutionary mechanisms of B cells in response to specific stimuli remains a significant challenge in the field of immunology. We introduce a new method, TRIBAL, which aims to infer the evolutionary history of clonally related B cells from scRNA-seq data. The key insight of TRIBAL is that inclusion of isotype data into the B cell lineage inference problem is valuable for reducing phylogenetic uncertainty that arises when only considering the receptor sequences. Consequently, the TRIBAL inferred B cell lineage trees jointly capture the somatic mutations introduced to the B cell receptor during affinity maturation and isotype transitions during class switch recombination. In addition, TRIBAL infers isotype transition probabilities that are valuable for gaining insight into the dynamics of class switching. Via