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Regional variation in the density of essential genes in mice.

ABSTRACT: In most species, and particularly in vertebrates, the percentage of genes absolutely required for survival, the essential genes, has not been estimated. To obtain this estimation, we used the mouse as an experimental model to carry out high-efficiency N-ethyl-N-nitrosourea (ENU) mutagenesis screens in two balancer chromosome regions, and compared our results to a third previously published screen. The number of essential genes in each region was predicted based on allele frequencies. We determined that the density of essential genes differs by up to an order of magnitude among genomic regions. This indicates that extrapolating from regional estimates to genome-wide estimates of essential genes has a huge variance. A particularly high density of essential genes on mouse Chromosome 11 coincides with a high degree of regional linkage conservation, providing a possible causal explanation for the density variation. This is the first demonstration of regional variation in essential gene density in the mouse genome.

SUBMITTER: Hentges KE

PROVIDER: S-EPMC1865562 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Regional variation in the density of essential genes in mice.

Hentges Kathryn E KE Pollock David D DD Liu Bin B Justice Monica J MJ

PLoS genetics 20070321 5

In most species, and particularly in vertebrates, the percentage of genes absolutely required for survival, the essential genes, has not been estimated. To obtain this estimation, we used the mouse as an experimental model to carry out high-efficiency N-ethyl-N-nitrosourea (ENU) mutagenesis screens in two balancer chromosome regions, and compared our results to a third previously published screen. The number of essential genes in each region was predicted based on allele frequencies. We determin ...[more]

PMID: 17480122

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Project description:MotivationProbabilistic Identification of bacterial essential genes using transposon-directed insertion-site sequencing (TraDIS) data based on Tn5 libraries has received relatively little attention in the literature; most methods are designed for mariner transposon insertions. Analysis of Tn5 transposon-based genomic data is challenging due to the high insertion density and genomic resolution. We present a novel probabilistic Bayesian approach for classifying bacterial essential genes using transposon insertion density derived from transposon insertion sequencing data. We implement a Markov chain Monte Carlo sampling procedure to estimate the posterior probability that any given gene is essential. We implement a Bayesian decision theory approach to selecting essential genes. We assess the effectiveness of our approach via analysis of both simulated data and three previously published Escherichia coli, Salmonella Typhimurium and Staphylococcus aureus datasets. These three bacteria have relatively well characterized essential genes which allows us to test our classification procedure using receiver operating characteristic curves and area under the curves. We compare the classification performance with that of Bio-Tradis, a standard tool for bacterial gene classification.ResultsOur method is able to classify genes in the three datasets with areas under the curves between 0.967 and 0.983. Our simulated synthetic datasets show that both the number of insertions and the extent to which insertions are tolerated in the distal regions of essential genes are both important in determining classification accuracy. Importantly our method gives the user the option of classifying essential genes based on the user-supplied costs of false discovery and false non-discovery.Availability and implementationAn R package that implements the method presented in this paper is available for download from https://github.com/Kevin-walters/insdens.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Regional variation in the density of essential genes in mice.

Publications

Regional variation in the density of essential genes in mice.

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