Large-Scale B Cell Receptor Sequence Analysis Using Phylogenetics and Machine Learning

Amrit Dhar

The adaptive immune system synthesizes antibodies, the soluble form of B cell receptors (BCRs), to bind to and neutralize pathogens that enter our body. B cells are able to generate a diverse set of high affinity antibodies through the affinity maturation process. During maturation, ``naive'' BCR sequences first accumulate mutations according to a neutral evolutionary process called somatic hypermutation (SHM), which may modify the associated binding affinities, and then are subject to natural selection by clonal expansion, which promotes the higher affinity antibodies. The set of mutated BCRs that result from a single naive BCR undergoing SHM can be referred to as a ``clonal family''. In this talk, I describe three projects that add to our understanding of BCR diversification and develop computational inference tools that work well in the presence of incompletely sampled data