Combining immune cell repertoire sequencing and functional expression with applications to autoimmune disease.

The cells of the adaptive immune system have the capacity to respond to a lifetime of diverse pathogens, in part due to somatic recombination of genes comprising the T and B cell receptors ([TB]CR). Several protocols now exist for simultaneously resolving [TB]CR identity and scRNAseq expression of all other polyadenalated mRNAs. I describe a pipeline for inferring *clonal* subpopulations of cells, that is, cells that share a [TB]CR from a common ancestor. This pipeline can scale to tens of thousands of cells. A series of statistical models are proposed for testing for expansion of specific clones in covariate groups, as well the omnibus propensity for clonal expansion. Lastly, I consider how [TB]CR identity can be combined with scRNAseq expression for unsupervised clustering using methods from multiview learning. I apply these methods to a data set of B cells isolated from the synovium of rheumatoid arthritis patients.Non UBCUnreviewedAuthor affiliation: University of RochesterResearche