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:	Ai, Shi-Meng, Gao, Jian-Jun, Liu, Shu-Qun, Fu, Yun-Xin
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534375/

id	pubmed-4534375
recordtype	oai_dc
spelling	pubmed-45343752015-08-24 Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square Ai, Shi-Meng Gao, Jian-Jun Liu, Shu-Qun Fu, Yun-Xin Research Article 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. Public Library of Science 2015-08-12 /pmc/articles/PMC4534375/ /pubmed/26266814 http://dx.doi.org/10.1371/journal.pone.0135398 Text en © 2015 Ai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ai, Shi-Meng Gao, Jian-Jun Liu, Shu-Qun Fu, Yun-Xin
spellingShingle	Ai, Shi-Meng Gao, Jian-Jun Liu, Shu-Qun Fu, Yun-Xin Efficient Estimation of Mutation Rates during Individual Development by Minimization of Chi-Square
author_facet	Ai, Shi-Meng Gao, Jian-Jun Liu, Shu-Qun Fu, Yun-Xin
author_sort	Ai, Shi-Meng
title	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_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_sort	efficient estimation of mutation rates during individual development by minimization of chi-square
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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534375/
_version_	1613258860415418368

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

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