Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.

Mutation primarily occurs when cells divide and it is highly desirable to have knowledge of the rate of mutations for each of the cell divisions during individual development. Recently, recessive lethal or nearly lethal mutations which were observed in a large mutation accumulation experiment using...

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Main Authors: Shi-Meng Ai, Jian-Jun Gao, Shu-Qun Liu, Yun-Xin Fu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4534375?pdf=render
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author Shi-Meng Ai
Jian-Jun Gao
Shu-Qun Liu
Yun-Xin Fu
author_facet Shi-Meng Ai
Jian-Jun Gao
Shu-Qun Liu
Yun-Xin Fu
author_sort Shi-Meng Ai
collection DOAJ
description Mutation primarily occurs when cells divide and it is highly desirable to have knowledge of the rate of mutations for each of the cell divisions during individual development. Recently, recessive lethal or nearly lethal mutations which were observed in a large mutation accumulation experiment using Drosophila melanogaster suggested that mutation rates vary significantly during the germline development of male Drosophila melanogaster. The analysis of the data was based on a combination of the maximum likelihood framework with numerical assistance from a newly developed coalescent algorithm. Although powerful, the likelihood based framework is computationally highly demanding which limited the scope of the inference. This paper presents a new estimation approach by minimizing chi-square statistics which is asymptotically consistent with the maximum likelihood method. When only at most one mutation in a family is considered the minimization of chi-square is simplified to a constrained weighted minimum least square method which can be solved easily by optimization theory. The new methods effectively eliminates the computational bottleneck of the likelihood. Reanalysis of the published Drosophila melanogaster mutation data results in similar estimates of mutation rates. The new method is also expected to be applicable to the analysis of mutation data generated by next-generation sequencing technology.
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spelling doaj.art-db0e9fa0e9b34c42b6df522765d76aad2022-12-22T03:16:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013539810.1371/journal.pone.0135398Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.Shi-Meng AiJian-Jun GaoShu-Qun LiuYun-Xin FuMutation primarily occurs when cells divide and it is highly desirable to have knowledge of the rate of mutations for each of the cell divisions during individual development. Recently, recessive lethal or nearly lethal mutations which were observed in a large mutation accumulation experiment using Drosophila melanogaster suggested that mutation rates vary significantly during the germline development of male Drosophila melanogaster. The analysis of the data was based on a combination of the maximum likelihood framework with numerical assistance from a newly developed coalescent algorithm. Although powerful, the likelihood based framework is computationally highly demanding which limited the scope of the inference. This paper presents a new estimation approach by minimizing chi-square statistics which is asymptotically consistent with the maximum likelihood method. When only at most one mutation in a family is considered the minimization of chi-square is simplified to a constrained weighted minimum least square method which can be solved easily by optimization theory. The new methods effectively eliminates the computational bottleneck of the likelihood. Reanalysis of the published Drosophila melanogaster mutation data results in similar estimates of mutation rates. The new method is also expected to be applicable to the analysis of mutation data generated by next-generation sequencing technology.http://europepmc.org/articles/PMC4534375?pdf=render
spellingShingle Shi-Meng Ai
Jian-Jun Gao
Shu-Qun Liu
Yun-Xin Fu
Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
PLoS ONE
title Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
title_full Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
title_fullStr Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
title_full_unstemmed Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
title_short Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square.
title_sort efficient estimation of mutation rates during individual development by minimization of chi square
url http://europepmc.org/articles/PMC4534375?pdf=render
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