PT  - JOURNAL ARTICLE
AU  - Joseph Kaplinsky
AU  - Ramy Arnaout
TI  - Robust Estimates of Overall Immune-Repertoire Diversity from High-Throughput Measurements on Samples
AID  - 10.1101/024612
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 024612
4099  - http://biorxiv.org/content/early/2015/08/13/024612.short
4100  - http://biorxiv.org/content/early/2015/08/13/024612.full
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.