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March 2019 Clonality: Point estimation
Lu Tian, Yi Liu, Andrew Z. Fire, Scott D. Boyd, Richard A. Olshen
Ann. Appl. Stat. 13(1): 113-131 (March 2019). DOI: 10.1214/18-AOAS1197

Abstract

Assessments of biological complexity for populations that are of mixed species are central in many biological contexts, including microbiomes, tumor cell population structure, and immune cell populations. Here we address the problem of quantifying the population diversity in experiments where high throughput DNA sequencing is used to distinguish a large number of cell subpopulations. Our model assumes a list of clonal species and their observed frequencies in each of several replicate sequencing libraries. Though the underlying distribution of frequencies cannot be estimated well from data coming from only a small fraction of the total cell population, one can estimate well the population-level clonality, defined as the sum of squared underlying fractions of the respective clones, the complement of the Gini–Simpson index. Specifically, we proposed to adaptively combine multiple unbiased estimators of clonality derived from pairs of replicates to construct a single estimator without relying on the commonly used but restrictive multinomial assumption. The new estimator performs particularly well for replicates of unequal size. We further illustrate the proposed methods with extensive simulations and a small real data example.

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Lu Tian. Yi Liu. Andrew Z. Fire. Scott D. Boyd. Richard A. Olshen. "Clonality: Point estimation." Ann. Appl. Stat. 13 (1) 113 - 131, March 2019. https://doi.org/10.1214/18-AOAS1197

Information

Received: 1 March 2017; Revised: 1 June 2018; Published: March 2019
First available in Project Euclid: 10 April 2019

zbMATH: 07057422
MathSciNet: MR3937423
Digital Object Identifier: 10.1214/18-AOAS1197

Rights: Copyright © 2019 Institute of Mathematical Statistics

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Vol.13 • No. 1 • March 2019
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