Dataset Information

Comparing DNA integration site clusters with scan statistics.

ABSTRACT:

Motivation

Gene therapy with retroviral vectors can induce adverse effects when those vectors integrate in sensitive genomic regions. Retroviral vectors are preferred that target sensitive regions less frequently, motivating the search for localized clusters of integration sites and comparison of the clusters formed by integration of different vectors. Scan statistics allow the discovery of spatial differences in clustering and calculation of false discovery rates providing statistical methods for comparing retroviral vectors.

Results

A scan statistic for comparing two vectors using multiple window widths is proposed with software to detect clustering differentials and compute false discovery rates. Application to several sets of experimentally determined HIV integration sites demonstrates the software. Simulated datasets of various sizes and signal strengths are used to determine the power to discover clusters and evaluate a convenient lower bound. This provides a toolkit for planning evaluations of new gene therapy vectors.

Availability and implementation

The geneRxCluster R package containing a simple tutorial and usage hints is available from http://www.bioconductor.org.

SUBMITTER: Berry CC

PROVIDER: S-EPMC4029028 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Comparing DNA integration site clusters with scan statistics.

Berry Charles C CC Ocwieja Karen E KE Malani Nirav N Bushman Frederic D FD

Bioinformatics (Oxford, England) 20140130 11

<h4>Motivation</h4>Gene therapy with retroviral vectors can induce adverse effects when those vectors integrate in sensitive genomic regions. Retroviral vectors are preferred that target sensitive regions less frequently, motivating the search for localized clusters of integration sites and comparison of the clusters formed by integration of different vectors. Scan statistics allow the discovery of spatial differences in clustering and calculation of false discovery rates providing statistical m ...[more]

PMID: 24489369

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Project description:BACKGROUND:Ageing is becoming a considerable public health burden in China, which produces great societal development challenges. Healthy and active longevity could ease the ageing burden on families and communities. To date, most studies of the oldest-old distribution are focused on a simple scale from spatial perspective, and the multi-scale spatio-temporal clusters trend in the oldest-old population has not yet been determined. Thus, the objective in present study is to use a new method to evaluate the spatio-temporal pattern and detect the risk clusters in the oldest-old population from three scales. METHODS:Individuals aged 65 years or older and individuals aged 80 years or older on three scales in China from 2000 to 2010 were used. The exploratory spatial data analysis was performed using Moran's I statistic, and the pattern of the oldest-old clusters among humans was examined by using the spatial scan statistical method. Then, spatial stratified heterogeneity was used to explore the factors affecting the spatial heterogeneity of the oldest-old population. RESULTS:The oldest-old index in the southeast coastal areas is higher than that in the northwest inland areas in China. A three-ladder terrain distribution of the oldest-old index from west to east is obvious. The overall pattern of the oldest-old index evolves from a "concave" shape to an "east-west uplift, and northern collapse" shape. Space-time analysis revealed that high-risk areas were concentrated in five regions: the Yangtze River Delta, the Pearl River Delta, the Southeast Coast, Sichuan and Chongqing, and the Central Plains. The oldest-old cluster at different scales shows a similar pattern, but local differences exist. The risk at the prefecture scale and county scale is greater than at the interprovincial scale; the sublevel can identify clusters that have not been identified at the previous level, especially the bordering areas of prefectures and counties; and more risk units and greater relative risk are found in urban areas than in rural areas. CONCLUSIONS:The results emphasized that spatial scan statistics can be used to estimate the spatial clusters of the oldest-old people. The detection of these clusters might be highly useful in the surveillance of the ageing phenomenon, thus helping local public health authorities measure the population burden at all locations, identifying geographical areas that require more attention, and evaluating the impacts of intervention programs.

Dataset Information

Comparing DNA integration site clusters with scan statistics.

Motivation

Results

Availability and implementation

Publications

Comparing DNA integration site clusters with scan statistics.

Similar Datasets

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