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

Banff International Research Station for Mathematical Innovation and Discovery

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.

Mathematics; Statistics; Computer science

video/mp4

Author affiliation: University of Rochester

2019-05-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/70067

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/