US Patent 10077478 Determining paired immune receptor chains from frequency matched subunits

The invention is directed to methods for determining nucleic acids that encode immune receptor chains originating from the same cell, that is, paired immune receptor chains. Methods of the invention comprise high-throughput sequencing of rearranged nucleic acids encoding immune receptors from one or more samples of lymphocytes. In one aspect, from a plurality of subsets of a sample, nucleic acids encoding separate chains of a pair are separately sequenced, wherein the size of the sample and the number of subsets are selected so that the distribution of lymphocytes approximates a binomial model. Paired chains are determined by identifying pairs that appear together or that are entirely absent in the subsets.