A0635
Title: A multi-bin rarefying method for evaluating alpha diversities in TCR sequencing data
Authors: Mo Li - UL at Lafayette (United States) [presenting]
Abstract: The purpose is to examine the impact of library size variation on T cell receptor (TCR) diversity analysis, specifically evaluating the commonly used overall rarefying method. Library sizes, reflected in sequencing experiment reads, vary significantly across samples, complicating alpha diversity estimation and comparison. Despite its common use, the overall rarefying method's effectiveness remains unverified. An innovative multi-bin rarefying approach is developed that partitions samples into multiple bins according to their library sizes, conducts rarefying within each bin for alpha diversity calculations, and performs meta-analysis across bins. Extensive simulations using real-world cytomegalovirus (CMV) data highlight the inadequacy of the overall rarefying approach in controlling the confounding effect of library size. The method proves robust in addressing library size confounding, outperforming competing normalization strategies by achieving better-controlled type-I error rates and enhanced statistical power in association tests.
