RT Journal Article SR Electronic T1 Robust Estimates of Overall Immune-Repertoire Diversity from High-Throughput Measurements on Samples JF bioRxiv FD Cold Spring Harbor Laboratory SP 024612 DO 10.1101/024612 A1 Joseph Kaplinsky A1 Ramy Arnaout YR 2015 UL http://biorxiv.org/content/early/2015/08/13/024612.abstract AB The diversity of a person’s B- and T-cell repertoires is both clinically important and a key measure of immunological complexity. However, diversity is hard to estimate by current methods due to inherent uncertainty in the number of B- and T-cell clones that will be missing from a blood or tissue sample by chance (the missing-species problem), inevitable sampling bias, and experimental noise. To address these problems we developed Recon, a maximum-likelihood method that reconstructs the clone-size distribution of an overall repertoire from measurements on a sample. Recon improves over previous work, enabling highly accurate estimates of overall diversity by any measure, including species richness and entropy, even at 0.03x coverage, with error bars. It also enables power calculations, allowing robust comparisons of diversity between individuals and over time. We apply Recon to in silico and experimental immune-repertoire sequencing datasets as proof of principle for measuring diversity in large, complex systems.